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Arterioles
Kinds of Arterioles Terms modified by Arterioles Selected AbstractsArteriolar Remodeling Following Ischemic Injury Extends from Capillary to Large Arteriole in the MicrocirculationMICROCIRCULATION, Issue 5 2008Alexander M. Bailey ABSTRACT Objective: Skeletal muscle vasculature undergoes arteriogenesis to restore tissue perfusion and function following loss of blood flow. This process has been shown to occur in large vessels following ischemia, although recent studies suggest this may occur in the microcirculation as well. We tested the hypothesis that ischemia induces microvascular remodeling in the skeletal muscle microcirculation on the scale of capillary to sub-35 ,m diameter arterioles. Methods: Ligations of a feeding arteriole to the caudal-half of the spinotrapezius muscle were performed on C57BL/6 mice. At 5 days, microvascular remodeling responses were quantified using intravital and whole-mount confocal microscopy. Immunohistochemistry was performed to visualize vessels, incorporated leukocytes, and regions of hypoxia. Results: Ischemic tissue underwent localized microvascular remodeling characteristic of arteriogenesis, including pronounced vessel tortuosity. In patent microvessels (diameters 15,35 ,m), we observed increases in vascular density (38%), branching (90%) and collateral development (36.5%). The formation of new arterioles (diameters 6,35 ,m) increased by 24.3%, while chronic hypoxia was absent from all tissues. Conclusions: Ischemic injury induces arteriogenesis in skeletal muscle microcirculation. Furthermore, this surgical model enables en face analysis of microcirculatory adaptations with single-cell resolution and can provide investigators with morphometric data on a microscale that is difficult to achieve using other models. [source] Vascular response to laser photothermolysis as a function of pulse duration, vessel type, and diameter: Implications for port wine stain laser therapyLASERS IN SURGERY AND MEDICINE, Issue 2 2002Sol Kimel PhD Abstract Background and Objective Treatment of port wine stains (PWS) by photothermolysis can be improved by optimizing laser parameters on an individual patient basis. We have studied the critical role of pulse duration (tp) on the treatment efficacy. Study Design/Materials and Methods The V-beam laser (Candela) allowed changing tp over user-specified discrete values between 1.5 and 40 milliseconds by delivering a series of 100 microsecond spikes. For the 1.5 and 3 millisecond pulses, three spikes were observed at intervals tp/2 and for tp,,,6 milliseconds, four spikes separated by tp/3. The ScleroPlus laser (Candela) has a smooth output over its fixed 1.5 milliseconds duration. Blood vessels in the chick chorioallantoic membrane (CAM) were irradiated at fixed wavelength (595 nm), spot size (7 mm), radiant exposure (15 Jcm,2), and at variable tp. The CAM contains an extensive microvascular network ranging from capillaries with diameter D,<,30 ,m to blood vessels of D,,,120 ,m. The CAM assay allows real-time video documentation, and observation of blood flow in pre-capillary arterioles (A) and post-capillary venules (V). Vessel injury was graded from recorded videotapes. Mathematical modeling was developed to interpret results of vessel injury when varying tp and D. A modified thermal relaxation time was introduced to calculate vessel wall temperature following laser exposure. Results Arterioles. For increasing tp, overall damage was found to decrease. For fixed tp, damage decreased with vessel size. Venules. For all D, damage was smaller than for corresponding arterioles. There was no dependence of damage on tp. For given tp, no variation of damage with D was observed. Photothermolysis due to spiked (V-beam) vs. smooth (Scleroplus) delivery of laser energy at fixed tp (1.5 milliseconds), showed similar vessel injuries for al values of D (P>0.05). Conclusions The difference between initial arteriole and venule damage could be explained by the threefold higher absorption coefficient at 595 nm in (oxygen-poor!) arterioles. In human patients, PWS consist of ectatic venules (characterized by higher absorption), so that these considerations favor the use of 595-nm irradiation for laser photothermolysis. For optimal treatment of PWS it is proposed that tp be between 0.1 and 1.5 milliseconds. This is based on a modified relaxation time ,d,, defined as the time required for heat conduction into the full thickness of the vessel wall, which is assumed to have a thickness ,D ,,0.1D. The corresponding ,d, will be a factor of about six smaller than given in the literature. For vessels with D between 30 and 300 ,m, ,d, ranges from 0.1 to 1.5 milliseconds. Lasers Surg. Med. 30:160,169, 2002. © 2002 Wiley-Liss, Inc. [source] Rapid Vasodilation in Isolated Skeletal Muscle Arterioles: Impact of Branch OrderMICROCIRCULATION, Issue 2 2010BRUNO T. ROSEGUINI Microcirculation (2010) 17, 1,11. doi: 10.1111/j.1549-8719.2009.00005.x Abstract We tested the hypothesis that segmental differences in the responsiveness and time course of vasodilation to metabolic signals putatively involved in rapid onset vasodilation (ROV) at the start of exercise exist within the skeletal muscle vasculature. Cannulated first-order (1As) and third-order arterioles (3As) of the rat gastrocnemius (G) muscle were exposed to cumulative doses of KCl, acetylcholine (Ach), or adenosine (Ado). In addition, time course and magnitude of vasodilation to localized application of these agonists were determined. 1As and 3As dilated similarly to incremental doses of the agonists. Continuous monitoring of internal diameter revealed a fast and transient dilatory response to microinjections of the agonists, with an average time delay (TD) before the onset of vasodilation of 2.8 ± 0.2 seconds (1As: 3.0 ± 0.3 seconds and 3As: 2.6 ± 0.3 seconds) and time-to-peak (TP) of 8.2 ± 0.7 seconds (1As: 10.3 ± 1 seconds and 3As:5.7 ± 0.5 seconds). No significant differences were detected for all parameters between 1As and 3As for KCl or Ado application, while 1As had a significantly longer TP and greater peak dilation than 3As to Ach. These findings demonstrate that 1As and 3As from the rat G muscle appear to have similar responsiveness to vasoactive agonists. Furthermore, the average TD before vasodilation supports a role for metabolic signals as contributors to the ROV. [source] The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-Brain Barrier PermeabilityMICROCIRCULATION, Issue 8 2009Marilyn J. Cipolla ABSTRACT Objective: We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability. Materials and Methods: Female ovariectomized Sprague-Dawley rats were replaced with estradiol (E2) and estriol (E3) (OVX + E;N=13) and compared to ovariectomized animals without replacement (OVX; N=14) and intact controls (CTL, proestrous; N=13). Passive and active diameters, percent tone, and passive distensibility of pressurized PA were compared. In addition, BBB permeability to Lucifer Yellow, a marker of transcellular transport, was compared in cerebral arteries. Results: Ovariectomy increased myogenic tone in PA, compared to CTL, that was not ameliorated by estrogen treatment. Percent tone at 75 mmHg for CTL vs. OVX and OVX + E was 44±3% vs. 51±1% and 54±3% (P<0.01 vs. CTL for both). No differences were found in passive diameters or distensibility between the groups. BBB permeability increased 500% in OVX vs. CTL animals; however, estrogen replacement restored barrier properties: flux of Lucifer Yellow for CTL, OVX, and OVX + E was (ng/mL): 3.4±1.2, 20.2±5.3 (P<0.01 vs. CTL), and 6.15±1.2 (n.s.). Conclusions: These results suggest that estrogen replacement may not be beneficial for small-vessel disease in the brain, but may limit BBB disruption and edema under conditions that cause it. [source] Reactivity of Brain Parenchymal Arterioles after Ischemia and ReperfusionMICROCIRCULATION, Issue 6 2008MARILYN J. CIPOLLA ABSTRACT Objective: We investigated the effect of ischemia and reperfusion on the vasoactive function of penetrating brain parenchymal arterioles under pressurized conditions. Methods: Parenchymal arterioles (<50 ,m in diameter) from within the middle cerebral artery territory were dissected from male Wistar rats that were either nonischemic control (n = 16) or ischemic for one hour and reperfused for 24 hours (n = 16) by temporary filament occlusion of the middle cerebral artery. Arterioles were mounted on glass cannulas within an arteriograph chamber that allowed for the measurement of lumen diameter and control over intravascular pressure. Results: After one hour of equilibration at 10 mmHg, spontaneous myogenic tone developed in both groups of animals, constricting control arterioles from 69 ± 9 to 49 ± 11 ,m (29.5 ± 10.2%) and ischemic arterioles from 66 ± 9 to 45 ± 11 ,m (33.1 ± 14.1%); p > 0.05. Contraction to the nitric oxide synthase inhibitor nitro-L-arginine (10,4M) was significantly diminished in ischemic arterioles, constricting only 3.2 ± 3.3 vs. 15.6 ± 12.5% in control arterioles (p = 0.017). Both groups dilated to nifedipine; however, the response was significantly diminished after ischemia. The EC50 for nifedipine in control arterioles was 3.54 ± 0.11 vs. 9.90 ± 0.71 nM for ischemic arterioles (p = 0.024). Conclusions: These findings demonstrate that functional changes occur in brain parenchymal arterioles after ischemia and reperfusion, a result that may significantly influence stroke outcome by altering blood flow to an ischemic region. [source] Extracellular Arginine Rapidly Dilates In Vivo Intestinal Arteries and Arterioles Through a Nitric Oxide MechanismMICROCIRCULATION, Issue 2 2008Laura Pezzuto ABSTRACT Objective: Arginine used for nitric oxide formation can be from intracellular stores or transported into cells. The study evaluated the rapidity, and primary site of NO and vascular resistance responses to arginine at near physiological concentrations (100,400 , M). Methods: Arginine was applied to a single arteriole through a micropipette to determine the fastest possible responses. For vascular blood flow and [NO] responses, arginine was added to the bathing media. Results: Dilation of single arterioles to arginine began in 10,15 seconds and application over the entire vasculature increased [NO] in , 60,90 seconds, and flow increased within 120,300 seconds. Resting periarteriolar [NO] for arterioles was 493.6 ± 30.5 nM and increased to 696.1 ± 68.2 and 820.1 ± 110.5 nM at 200 and 400 , M L-arginine. The blood flow increased 50% at 400,1200 , M L-arginine. The reduced arterial resistance during topical arginine was significantly greater than microvascular resistance at 100 and 200 , M arginine. All responses were blocked by L-NAME. Conclusions: This study demonstrated arterial resistance responses are as or more responsive to arginine induced NO formation as arterioles at near physiological concentrations of arginine. The vascular NO and resistance responses occurred rapidly at L-arginine concentrations at and below 400 , M, which predict arginine transport processes were involved. [source] Inhibition of NAD(P)H Oxidase Alleviates Impaired NOS-dependent Responses of Pial Arterioles in Type 1 Diabetes MellitusMICROCIRCULATION, Issue 7 2006WILLIAM G. MAYHAN ABSTRACT Objective: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). Methods: In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. Results: Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. Conclusions: The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase. [source] Membrane Hyperpolarization Is Not Required for Sustained Muscarinic Agonist-Induced Increases in Intracellular Ca2+ in Arteriolar Endothelial CellsMICROCIRCULATION, Issue 2 2005KENNETH D. COHEN ABSTRACT Objective: Hyperpolarization modulates Ca2+ influx during agonist stimulation in many endothelial cells, but the effects of hyperpolarization on Ca2+ influx in freshly isolated arteriolar endothelial cells are unknown. Therefore, the purpose of the present study was to characterize agonist-induced Ca2+ transients in freshly isolated arteriolar endothelial cells and to test the hypothesis that membrane hyperpolarization augments agonist-induced Ca2+ influx into these cells. Methods: Arterioles were removed from hamster cremaster muscles and arteriolar endothelial cells were enzymatically isolated. Endothelial cells were loaded with Fura 2-AM and the Fura 2 ratio measured photometrically as an index of intracellular Ca2+. The cells were then stimulated with the muscarinic, cholinergic agonist, methacholine, and the resulting Ca2+ transients were measured. Results: Methacholine (1 , M) increased the endothelial cell Fura 2 ratio from a baseline of 0.81 ± 0.02 to an initial peak of 1.17 ± 0.05 (n = 17) followed by a sustained plateau of 1.12 ± 0.07. The plateau phase of the Ca2+ transient was inhibited by removal of extracellular Ca2+ (n = 12, p < .05), or the nonselective cation channel blockers Gd3+ (30 , M; n = 7, p < .05) or La3+ (50 , M; n = 7, p < .05) without significant effect on the baseline or peak (p > .05). The initial peak of methacholine-induced Ca2+ transients was inhibited by the IP3 -receptor antagonist xestospongin D (10 , M, n = 5, p < .05). The methacholine-induced Ca2+ transients were accompanied by endothelial cell hyperpolarization of approximately 14,18 mV, as assessed by experiments using the potentiometric dye, di-8-ANEPPS as well as by patch-clamp experiments. However, inhibition of hyperpolarization by blockade of Ca2+ -activated K+ channels with charybdotoxin (100 nM) and apamin (100 nM) (n = 5), or exposure of endothelial cells to 80 or 145 mM KCl (both n = 7) had no effect on the plateau phase of methacholine-induced Ca2+ transients (p > .05). Conclusions: Freshly isolated arteriolar endothelial cells display agonist-induced Ca2+ transients. For the muscarinic agonist, methacholine, these Ca2+ transients result from release of Ca2+ from intracellular stores through IP3 receptors, followed by sustained influx of extracellular Ca2+. While these changes in intracellular Ca2+ are associated with endothelial cell hyperpolarization, the methacholine-induced, sustained increase in intracellular Ca2+ appears to be independent from this change in membrane potential. These data suggest that arteriolar endothelial cells may possess a novel Ca2+ influx pathway, or that the relationship between intracellular Ca2+ and Ca2+ influx is more complex than that observed in other endothelial cells. [source] Calcium handling in afferent arteriolesACTA PHYSIOLOGICA, Issue 4 2004M. Salomonsson Abstract The cytosolic intracellular calcium concentration ([Ca2+]i) is a major determining factor in the vascular smooth muscle tone. In the afferent arteriole it has been shown that agonists utilizing G-protein coupled receptors recruit Ca2+ via release from intracellular stores and entry via pathways in the plasma membrane. The relative importances of entry vs. mobilization seem to differ between different agonists, species and preparations. The entry pathway might include different types of voltage sensitive Ca2+ channels located in the plasmalemma such as dihydropyridine sensitive L-type channels, T-type channels and P/Q channels. A role for non-voltage sensitive entry pathways has also been suggested. The importance of voltage sensitive Ca2+ channels in the control of the tone of the afferent arteriole (and thus in the control of renal function and whole body control of extracellular fluid volume and blood pressure) sheds light on the control of the membrane potential of afferent arteriolar smooth muscle cells. Thus, K+ and Cl, channels are of importance in their role as major determinants of membrane potential. Some studies suggest a role for calcium-activated chloride (ClCa) channels in the renal vasoconstriction elicited by agonists. Other investigators have found evidence for several types of K+ channels in the regulation of the afferent arteriolar tone. The available literature in this field regarding afferent arterioles is, however, relatively sparse and not conclusive. This review is an attempt to summarize the results obtained by others and ourselves in the field of agonist induced afferent arteriolar Ca2+ recruitment, with special emphasis on the control of voltage sensitive Ca2+ entry. Outline of the Manuscript: This manuscript is structured as follows: it begins with an introduction where the general role for [Ca2+]i as a key factor in the regulation of the tone of vascular smooth muscles (VSMC) is detailed. In this section there is an emphasis is on observations that could be attributed to afferent arteriolar function. We then investigate the literature and describe our results regarding the relative roles for Ca2+ entry and intracellular release in afferent arterioles in response to vasoactive agents, with the focus on noradrenalin (NA) and angiotensin II (Ang II). Finally, we examine the role of ion channels (i.e. K+ and Cl, channels) for the membrane potential, and thus activation of voltage sensitive Ca2+ channels. [source] The vasodilatory actions of insulin on resistance and terminal arterioles and their impact on muscle glucose uptakeDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2004Lucy H. Clerk Abstract Whether a discrete vascular action of insulin in skeletal muscle integrally participates in insulin-mediated glucose disposal has been extensively examined but remains a contentious issue. Here, we review some of the data both supporting and questioning the role of insulin-mediated increases in limb blood flow in glucose metabolism. We advance the hypothesis that controversy has arisen, at least in part, from a failure to recognize that insulin exerts at least three separate actions on the peripheral vasculature, each with its own characteristic dose and time responsiveness. We summarize how, viewed in this manner, certain points of contention can be resolved. We also advance the hypothesis that an action on the precapillary arteriole may play the dominant role in mediating perfusion-dependent effects of insulin on glucose metabolism in muscle. Copyright © 2003 John Wiley & Sons, Ltd. [source] Inhibition of localized thrombosis in P2Y1 -deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonistJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2003N. Lenain Summary., Previous studies in experimental models revealed a role for the P2Y1 platelet ADP receptor in systemic vascular thromboembolism models. In the present work, we used models of localized arterial and venous thrombosis to assess the role of the P2Y1 receptor in these processes. Arterial thrombosis was induced in one mesenteric arteriole of a mouse using FeCl3, while venous thrombosis was studied in a Wessler model adapted to rats. P2Y1 -deficient mice and mice treated with the P2Y1 antagonist MRS2179 displayed significantly less arterial thrombosis than their respective controls. Combination of P2Y1 deficiency with P2Y12 inhibition led to a significant additive effect. Venous thrombosis was slightly but significantly inhibited in MRS2179-treated rats. These results demonstrate a role for the P2Y1 receptor in both arterial and venous thrombosis, further establishing this receptor as a potential target for antithrombotic drugs. [source] Vascular response to laser photothermolysis as a function of pulse duration, vessel type, and diameter: Implications for port wine stain laser therapyLASERS IN SURGERY AND MEDICINE, Issue 2 2002Sol Kimel PhD Abstract Background and Objective Treatment of port wine stains (PWS) by photothermolysis can be improved by optimizing laser parameters on an individual patient basis. We have studied the critical role of pulse duration (tp) on the treatment efficacy. Study Design/Materials and Methods The V-beam laser (Candela) allowed changing tp over user-specified discrete values between 1.5 and 40 milliseconds by delivering a series of 100 microsecond spikes. For the 1.5 and 3 millisecond pulses, three spikes were observed at intervals tp/2 and for tp,,,6 milliseconds, four spikes separated by tp/3. The ScleroPlus laser (Candela) has a smooth output over its fixed 1.5 milliseconds duration. Blood vessels in the chick chorioallantoic membrane (CAM) were irradiated at fixed wavelength (595 nm), spot size (7 mm), radiant exposure (15 Jcm,2), and at variable tp. The CAM contains an extensive microvascular network ranging from capillaries with diameter D,<,30 ,m to blood vessels of D,,,120 ,m. The CAM assay allows real-time video documentation, and observation of blood flow in pre-capillary arterioles (A) and post-capillary venules (V). Vessel injury was graded from recorded videotapes. Mathematical modeling was developed to interpret results of vessel injury when varying tp and D. A modified thermal relaxation time was introduced to calculate vessel wall temperature following laser exposure. Results Arterioles. For increasing tp, overall damage was found to decrease. For fixed tp, damage decreased with vessel size. Venules. For all D, damage was smaller than for corresponding arterioles. There was no dependence of damage on tp. For given tp, no variation of damage with D was observed. Photothermolysis due to spiked (V-beam) vs. smooth (Scleroplus) delivery of laser energy at fixed tp (1.5 milliseconds), showed similar vessel injuries for al values of D (P>0.05). Conclusions The difference between initial arteriole and venule damage could be explained by the threefold higher absorption coefficient at 595 nm in (oxygen-poor!) arterioles. In human patients, PWS consist of ectatic venules (characterized by higher absorption), so that these considerations favor the use of 595-nm irradiation for laser photothermolysis. For optimal treatment of PWS it is proposed that tp be between 0.1 and 1.5 milliseconds. This is based on a modified relaxation time ,d,, defined as the time required for heat conduction into the full thickness of the vessel wall, which is assumed to have a thickness ,D ,,0.1D. The corresponding ,d, will be a factor of about six smaller than given in the literature. For vessels with D between 30 and 300 ,m, ,d, ranges from 0.1 to 1.5 milliseconds. Lasers Surg. Med. 30:160,169, 2002. © 2002 Wiley-Liss, Inc. [source] Arteriolar Remodeling Following Ischemic Injury Extends from Capillary to Large Arteriole in the MicrocirculationMICROCIRCULATION, Issue 5 2008Alexander M. Bailey ABSTRACT Objective: Skeletal muscle vasculature undergoes arteriogenesis to restore tissue perfusion and function following loss of blood flow. This process has been shown to occur in large vessels following ischemia, although recent studies suggest this may occur in the microcirculation as well. We tested the hypothesis that ischemia induces microvascular remodeling in the skeletal muscle microcirculation on the scale of capillary to sub-35 ,m diameter arterioles. Methods: Ligations of a feeding arteriole to the caudal-half of the spinotrapezius muscle were performed on C57BL/6 mice. At 5 days, microvascular remodeling responses were quantified using intravital and whole-mount confocal microscopy. Immunohistochemistry was performed to visualize vessels, incorporated leukocytes, and regions of hypoxia. Results: Ischemic tissue underwent localized microvascular remodeling characteristic of arteriogenesis, including pronounced vessel tortuosity. In patent microvessels (diameters 15,35 ,m), we observed increases in vascular density (38%), branching (90%) and collateral development (36.5%). The formation of new arterioles (diameters 6,35 ,m) increased by 24.3%, while chronic hypoxia was absent from all tissues. Conclusions: Ischemic injury induces arteriogenesis in skeletal muscle microcirculation. Furthermore, this surgical model enables en face analysis of microcirculatory adaptations with single-cell resolution and can provide investigators with morphometric data on a microscale that is difficult to achieve using other models. [source] Longitudinal and Radial Gradients of PO2 in the Hamster Cheek Pouch MicrocirculationMICROCIRCULATION, Issue 3 2008Helena Carvalho ABSTRACT Objectives: The aim of this study was to determine longitudinal and radial gradients in oxygen tension (PO2) in microvessels of the hamster cheek pouch. Methods: We measured PO2 using the phosphorescence-quenching method in two orders of arterioles (45.8 ± 5.5 and 19.9 ± 1.8 , m diameter), capillaries, and two orders of venules (50.5 ± 3.4 and 21.4 ± 2.0 , m diameter) in order to determine the longitudinal PO2 gradient. At the arteriolar and venular sites, we also measured PO2 at four different sites for an analysis of radial PO2 gradients: centerline, inside wall (larger arteriole and venule only), outside wall, and interstitium. We used 10 hamsters weighing 115 ± 27 g anesthetized with pentobarbital intraperitoneally and maintained with alpha-chloralose intravenously. The cheek pouch was everted and a single-layered preparation was studied by intravital microscopy. Albumin-bound Pd-porphyrin was infused into the circulation and excited by flash illumination at 10 Hz, with a rectangular diaphragm limiting the excitation field to 5 × 25 , m. Results: In the longitudinal direction, intravascular PO2 decreased significantly (P < 0.01) from large arterioles (39.5 ± 2.3 mmHg) to small arterioles (32.2 ± 0.3 mmHg), then to capillaries (30.2 ± 1.8 mmHg), and on to small venules (27.3 ± 2.1 mmHg) and large venules (25.5 ± 2.2 mmHg). In the radial direction, PO2 decreased significantly (P < 0.01) in and around larger arterioles, and to a lesser extent, around the smaller ones (P < 0.05). There was no significant PO2 gradient, longitudinal or radial, associated with venules. The PO2 difference from the centerline to the outside wall in large arterioles was 8.3 ± 1.4 mmHg, and most of the decline in PO2 in the radial direction was contributed by the intravascular difference (4.7 ± 2.1 mmHg) and only about 1.0 ± 2.7 mmHg by the transmural difference. Conclusions: Our data show that there are large intra-arteriolar radial PO2 gradients, but no large transmural PO2 differences, suggesting that the oxygen consumption of the microvessel wall is not exceptionally high. [source] Extracellular Arginine Rapidly Dilates In Vivo Intestinal Arteries and Arterioles Through a Nitric Oxide MechanismMICROCIRCULATION, Issue 2 2008Laura Pezzuto ABSTRACT Objective: Arginine used for nitric oxide formation can be from intracellular stores or transported into cells. The study evaluated the rapidity, and primary site of NO and vascular resistance responses to arginine at near physiological concentrations (100,400 , M). Methods: Arginine was applied to a single arteriole through a micropipette to determine the fastest possible responses. For vascular blood flow and [NO] responses, arginine was added to the bathing media. Results: Dilation of single arterioles to arginine began in 10,15 seconds and application over the entire vasculature increased [NO] in , 60,90 seconds, and flow increased within 120,300 seconds. Resting periarteriolar [NO] for arterioles was 493.6 ± 30.5 nM and increased to 696.1 ± 68.2 and 820.1 ± 110.5 nM at 200 and 400 , M L-arginine. The blood flow increased 50% at 400,1200 , M L-arginine. The reduced arterial resistance during topical arginine was significantly greater than microvascular resistance at 100 and 200 , M arginine. All responses were blocked by L-NAME. Conclusions: This study demonstrated arterial resistance responses are as or more responsive to arginine induced NO formation as arterioles at near physiological concentrations of arginine. The vascular NO and resistance responses occurred rapidly at L-arginine concentrations at and below 400 , M, which predict arginine transport processes were involved. [source] Neurovascular Alignment in Adult Mouse Skeletal MusclesMICROCIRCULATION, Issue 2 2005SHAWN E. BEARDEN ABSTRACT Objective: Muscle blood flow increases with motor unit recruitment. The physical relationships between somatic motor nerves, which control muscle fiber contraction, and arterioles, which control microvascular perfusion, are unexplored. The authors tested the hypothesis that motor axons align with arterioles in adult skeletal muscle. Methods: Transgenic mice (C57BL/6 background, n = 5; 10 months of age) expressing yellow fluorescent protein in all motor nerves underwent vascular casting (Microfil). Excised epitrochlearis, gracilis, gluteus maximus, and spinotrapezius muscles were imaged at 380× and 760× and a computer-integrated tracing system (Neurolucida) was used to acquire 3-dimensional digital renderings of entire arteriolar and neural networks within each muscle. Results: Arteriolar networks were typically ,3-fold longer than neural networks. Nerves coursed with arterioles until terminating at motor endplates. Across muscles, proximity analyses revealed that , 75% of total nerve length (9.8,48.8 mm) lay within 200 ,m of the nearest arteriole (diameters of 15,60 , m). Conclusions: Somatic motor nerves and arterioles align closely within adult mammalian skeletal muscle. Understanding the signals governing neurovascular alignment may hold important clues for the advancement of tissue engineering and regeneration. [source] Upregulation of immunoreactivity of endothelin-1 and ,-SMA in PDL microvasculature following acute tooth loading: an immunohistochemical study in the marmosetORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 2 2003MR Sims Structured Abstract Authors , Sims MR, Ashworth JF, Sampson WJ Objectives , To test the hypothesis that a continuous mechanical tooth load would elevate immunoreactivity of endothelin-1 (ET-1) and alpha-smooth muscle actin (,-SMA) in the periodontal ligament (PDL) microvasculature. Design , A randomized control study employing 1.5 h of loading to first molars. Setting and Sample Population , Orthodontic Research Laboratory, Dental School, Adelaide University. Four young adult, male marmoset monkeys were consecutively anaesthetized and treated. Experimental Variable , An external telescoping frame applied a jaw closing load (120,200 g) transmitted occlusally, via a rubber pad, to randomly assigned mandibular left or right first molars. Contralateral molars were used as controls. Outcome Measure , Undemineralized, midsagittal, mandibular molar slices, ,150 ,m thick were immunolabelled with ET-1 and ,-SMA antibodies and examined in a confocal laser scanning microscope (CLSM) for vascular endothelium and smooth muscle immunolabelling. Results , Three categories of post-capillary-sized venule endothelial cell immunolabelling occurred: endothelium labelled solely with ET-1; endothelium labelled solely with ,-SMA; endothelium labelled with both ET-1 and ,-SMA. In endothelial cells, the ,-SMA showed a moderate cytoplasmic distribution with dense peripheral concentration. Loading increased arteriole ,-SMA actin labelling. Conclusion , Scattered expression of ET-1 is the default state in primate PDL endothelial cells. Increased antigenicity of endothelial cells to both ET-1 and ,-SMA, and of arteriolar smooth muscle to ,-SMA, is a response to shear and compression loads. [source] Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB1 and VR1 receptorsBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2006L Moezi Background and purpose: Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB1 antagonist), AM630 (CB2 antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis. Experimental approach: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB1, CB2 and VR1 receptor expression in SMA was assessed by western blot and RT-PCR. Key results: Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB1 and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group. Conclusions and implications: These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB1 - and VR1-mediated mechanisms. British Journal of Pharmacology (2006) 149, 898,908. doi:10.1038/sj.bjp.0706928 [source] 2424: Pulsatile haemodynamics: potential for end-organ damage?ACTA OPHTHALMOLOGICA, Issue 2010C HUDSON Purpose Increases in velocity pulse wave amplitude, or max:min velocity ratio, represent early haemodynamic disturbances associated with diabetic retinopathy (DR) and age-related macular degeneration. This change reflects an increase in vessel wall rigidity that is generally accepted to occur in the central vasculature but the peripheral vasculature is also implicated in this process. This presentation will highlight the implications of these changes in terms of end-organ damage in DR. Methods The sample comprised 4 groups: Group 1: 50 non-diabetic control subjects. Group 2: 56 diabetic patients without clinically visible DR. Group 3: 54 diabetic patients with micro-aneurysms and / or hard exudates within 2 disc diameters of the fovea in the absence of clinically manifest diabetic macular edema (DME). Group 4: 40 patients with clinically manifest DME. The diabetic patients were predominantly type 2. Retinal hemodynamics were assessed in the superior temporal retinal arteriole using the Canon Laser Blood Flowmeter. Intraocular pressure, blood pressure and relevant systemic markers of diabetes control and complications were also assessed. Results The velocity pulse wave amplitude was elevated with increasing risk of DME (p<0.0001). No significant differences were found between the groups with respect to diameter, velocity or flow. Pulse wave amplitude was correlated to age, duration of diabetes, blood pressure, pulse rate, IOP and serum potassium levels. Conclusion The increase in velocity pulse wave amplitude will induce excessive pressure pulsatility in the retinal arterioles and capillaries, changes in vascular function (e.g. loss of vascular regulation) and changes in vessel structure. Commercial interest [source] 2321: Retinal vessel diameter affects oxygen saturation measurementsACTA OPHTHALMOLOGICA, Issue 2010SH HARDARSON Purpose To test whether retinal vessel oxygen saturation measurements are affected by vessel diameter and to compare saturation between the temporal and nasal retina. Methods The Oxymap retinal oximeter is based on a fundus camera. It measures light absorbance at two wavelengths of light and calculates oxygen saturation in retinal vessels as well as vessel diameter. Measurements were performed on 12 healthy individuals. The effect of vessel diameter on saturation measurements was tested by measuring before and after the first bifurcation in the retina (1st degree parent vessels and 2nd degree daughter vessels). Arteriolar saturation can be assumed to be equal before and after bifurcation. Results The ratio between oxygen saturation in 1st degree parent arteriole and 2nd degree daughter arteriole was 0.97±0.02 (mean±SD). The ratio was significantly lower than the theoretical value of 1.00 (p<0.001, n=12) The corresponding ratio for venules was 0.90±0.04 (p<0.001). Oxygen saturation was 94±6% in 1st degree superotemporal arterioles and 99±6% in superonasal arterioles (p=0.057). Oxygen saturation in inferotemporal arterioles was 89±6% and 95±4% in inferonasal arterioles (p=0.009). There was no significant difference in venous saturation between temporal and nasal quadrants. Conclusion Measured oxygen saturation is lower in 1st degree parent vessels than in their 2nd degree daughter branches. This indicates that retinal vessel diameter affects oxygen saturation measurements. The higher measured saturation in the nasal arterioles, compared to temporal arterioles, may also be due to the fact that the nasal vessels are narrower. A correction for the effect of vessel diameter should be incorporated into oxygen saturation measurements. Commercial interest [source] Retinal oxygenation in diabetic retinopathyACTA OPHTHALMOLOGICA, Issue 2009SH HARDARSON Purpose Diabetic retinopathy (DR) is believed to cause retinal tissue hypoxia by damaging retinal capillaries. The purpose of this study was to examine the effect of diabetic retinopathy on oxygen saturation in retinal arterioles and venules. Methods The retinal oximeter (Oxymap ehf., Reykjavik, Iceland) is composed of a fundus camera, beam splitter and light filters. Specialized software calculates relative oxygen saturation from light absorption at two wavelengths of light (605nm and 586nm). One first or second degree temporal arteriole and venule were measured in one eye of 31 healthy individual and 28 patients with diabetic retinopathy. The diabetic patients had background DR (n=6), macular oedema (n=7), untreated preproliferative or proliferative DR (n=7) or stable proliferative DR after treatment (n=8). Statistical analyses were performed with an unpaired t-test, one-way ANOVA and Dunnett's post test. Results Retinal arteriolar saturation was 93±4% (n=31, mean±SD) in healthy subjects and 101±6% (n=28) in patients with DR (p<0.0001). Retinal venular saturation was 58±6% in healthy subjects and 67±8% in diabetic patients (p<0.0001). Arteriolar and venular saturation was higher in all subgroups of diabetic patients (see methods) than in healthy subjects. Conclusion Increased oxygen saturation in retinal vessels in diabetic retinopathy, also found by other researchers, is consistent with poor distribution of blood and oxygen to the retinal tissue rather than decreased total retinal blood flow. Poor distribution of oxygen may be caused by capillary dropouts and shunts as well as thickening of the capillary walls. Commercial interest [source] Communication:Dual macroaneurysms on the same retinal arterioleCLINICAL AND EXPERIMENTAL OPTOMETRY, Issue 2 2005Mark A DePaola BOptom ABSTRACT A case of two macroaneurysms on the same retinal arteriole is presented. After observation of these lesions for some weeks, an increased threat to the macula from oedema led to laser photocoagulation. Although treatment did not hasten resolution, the patient has remained asymptomatic. The aetiology and natural history of macroaneurysms are discussed. [source] DIFFERENTIAL NEURAL CONTROL OF GLOMERULAR ULTRAFILTRATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2004Kate M Denton Summary 1.,The renal nerves constrict the renal vasculature, causing decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Whether renal haemodynamics are influenced by changes in renal nerve activity within the physiological range is a matter of debate. 2.,We have identified two morphologically distinct populations of nerves within the kidney, which are differentially distributed to the renal afferent and efferent arterioles. Type I nerves almost exclusively innervate the afferent arteriole whereas type II nerves are distributed equally on the afferent and efferent arterioles. We have also demonstrated that type II nerves are immunoreactive for neuropeptide Y, whereas type I nerves are not. 3.,This led us to hypothesize that, in the kidney, distinct populations of nerves innervate specific effector tissues and that these nerves may be selectively activated, setting the basis for the differential neural control of GFR. In physiological studies, we demonstrated that differential changes in glomerular capillary pressure occurred in response to graded reflex activation of the renal nerves, compatible with our hypothesis. 4.,Thus, sympathetic outflow may be capable of selectively increasing or decreasing glomerular capillary pressure and, hence, GFR by differentially activating separate populations of renal nerves. This has important implications for our understanding of the neural control of body fluid balance in health and disease. [source] Angiotensin II enhances the afferent arteriolar response to adenosine through increases in cytosolic calciumACTA PHYSIOLOGICA, Issue 4 2009E. Y. Lai Abstract Aims:, Angiotensin II (Ang II) is a strong renal vasoconstrictor and modulates the tubuloglomerular feedback (TGF). We hypothesized that Ang II at low concentrations enhances the vasoconstrictor effect of adenosine (Ado), the mediator of TGF. Methods:, Afferent arterioles of mice were isolated and perfused, and both isotonic contractions and cytosolic calcium transients were measured. Results:, Bolus application of Ang II (10,12 and 10,10 m) induced negligible vasoconstrictions, while Ang II at 10,8 m reduced diameters by 35%. Ang II at 10,12, 10,10 and 10,8 m clearly enhanced the arteriolar response to cumulative applications of Ado (10,11 to 10,4 m). Ado application increased the cytosolic calcium concentrations in the vascular smooth muscle, which were higher at 10,5 m than at 10,8 m. Ang II (10,11 to 10,6 m) also induced concentration-dependent calcium transients, which were attenuated by AT1 receptor inhibition. Simultaneously applied Ang II (10,10 m) additively enhanced the calcium transients induced by 10,8 and 10,5 m Ado. The transients were partly inhibited by AT1 or A1 receptor antagonists, but not significantly by A2 receptor antagonists. Conclusion:, A low dose of Ang II enhances Ado-induced constrictions, partly via AT1 receptor-mediated calcium increase. Ado increases intracellular calcium by acting on A1 but not A2 receptors. The potentiating effect of Ang II on Ado-induced arteriolar vasoconstrictions may involve calcium sensitization of the contractile machinery, as Ang II only additively increased cytosolic calcium concentrations, while its effect on the arteriolar constriction was more than additive. The potentiating effect of Ang II might contribute to the resetting of TGF. [source] Calcium handling in afferent arteriolesACTA PHYSIOLOGICA, Issue 4 2004M. Salomonsson Abstract The cytosolic intracellular calcium concentration ([Ca2+]i) is a major determining factor in the vascular smooth muscle tone. In the afferent arteriole it has been shown that agonists utilizing G-protein coupled receptors recruit Ca2+ via release from intracellular stores and entry via pathways in the plasma membrane. The relative importances of entry vs. mobilization seem to differ between different agonists, species and preparations. The entry pathway might include different types of voltage sensitive Ca2+ channels located in the plasmalemma such as dihydropyridine sensitive L-type channels, T-type channels and P/Q channels. A role for non-voltage sensitive entry pathways has also been suggested. The importance of voltage sensitive Ca2+ channels in the control of the tone of the afferent arteriole (and thus in the control of renal function and whole body control of extracellular fluid volume and blood pressure) sheds light on the control of the membrane potential of afferent arteriolar smooth muscle cells. Thus, K+ and Cl, channels are of importance in their role as major determinants of membrane potential. Some studies suggest a role for calcium-activated chloride (ClCa) channels in the renal vasoconstriction elicited by agonists. Other investigators have found evidence for several types of K+ channels in the regulation of the afferent arteriolar tone. The available literature in this field regarding afferent arterioles is, however, relatively sparse and not conclusive. This review is an attempt to summarize the results obtained by others and ourselves in the field of agonist induced afferent arteriolar Ca2+ recruitment, with special emphasis on the control of voltage sensitive Ca2+ entry. Outline of the Manuscript: This manuscript is structured as follows: it begins with an introduction where the general role for [Ca2+]i as a key factor in the regulation of the tone of vascular smooth muscles (VSMC) is detailed. In this section there is an emphasis is on observations that could be attributed to afferent arteriolar function. We then investigate the literature and describe our results regarding the relative roles for Ca2+ entry and intracellular release in afferent arterioles in response to vasoactive agents, with the focus on noradrenalin (NA) and angiotensin II (Ang II). Finally, we examine the role of ion channels (i.e. K+ and Cl, channels) for the membrane potential, and thus activation of voltage sensitive Ca2+ channels. [source] Nitric oxide counteracts angiotensin II induced contraction in efferent arterioles in miceACTA PHYSIOLOGICA, Issue 4 2004A. Patzak Abstract Aim:, Efferent arterioles (Ef) are one of the final control elements in glomerular haemodynamics. The influence of nitric oxide (NO) on Ef remains ambiguous. Methods:, To test the hypothesis that endothelial NO plays an important role in this context, afferent arterioles (Af) and Ef of wild-type mice (WT), and Ef of mice lacking the endothelial NO synthetase [eNOS(,/,)] were perfused. Perfusion was performed in Ef via Af (orthograde) as well as from the distal end of Ef (retrograde), which provides an estimate for the importance of substances derived from the glomerulus. Angiotensin II (Ang II) was added in doses ranging from 10,12 to 10,6 mol L,1 to the bath solution. Results:, Ang II reduced the luminal diameter of Af to 68 ± 7 and in Ef to 55 ± 8% during orthograde, and to 35 ± 6% during retrograde perfusion (10,6 mol L,1 Ang II) in WT. Pre-treatment with NG -Nitro- l -arginine-methylester (l -NAME) (10,4 mol L,1) increased the Ang II sensitivity in retrograde (17 ± 9%) and orthograde perfused Ef (19 ± 9%). The Ang II sensitivity was enhanced in eNOS(,/,) mice compared with WT, too. Already at a dose of Ang II 10,9 mol L,1, luminal diameters diminished to 8 ± 7 and 7 ± 4%. Conclusion:, The increased Ang II sensitivity during l -NAME pre-treatment and in eNOS(,/,) mice indicates a strong counteraction of endothelial derived NO on Ang II induced contraction in Ef. Moreover, Ef are similarly sensitive to Ang II during either retrograde or orthograde perfusion in the absence of NO effects, suggesting that NO mediates, at least in part, the action of potential vasodilatory substances from the glomerulus. [source] 5-Hydroxytryptamine-induced microvascular pressure transients in lungs of anaesthetized rabbitsACTA PHYSIOLOGICA, Issue 2 2001N. Sen We determined lung microvascular pressure transients induced by 5-hydroxytryptamine (5HT), by the micropuncture technique. We mechanically ventilated anaesthetized (halothane 0.8%), open-chested rabbits, in which we recorded pulmonary artery (PA), left atrial (LA) and carotid artery pressures and cardiac output. For 4-min periods of stopped ventilation, we constantly inflated the lung with airway pressure of 7 cmH2O, then micropunctured the lung to determine pressures in arterioles and venules of 20,25 ,m diameter. An intravenous bolus infusion of 5HT (100 ,g), increased total pulmonary vascular resistance by 59%. Prior to 5HT infusion, the arterial, microvascular and venous segments comprised 30, 50 and 19% of the total pulmonary vascular pressure drop, respectively. However 14 s after 5HT infusion, the PA-arteriole pressure difference (arterial pressure drop) increased 46%, while the venule-LA pressure difference (venous pressure drop) increased >100%. The arteriole,venule pressure difference (microvascular pressure drop) was abolished. The increase in the arterial pressure drop was maintained for 4.8 min, whereas the increased venous pressure drop reverted to baseline in <1 min. We conclude that in the rabbit lung in situ, a 5HT bolus causes sustained arterial constriction and a strong but transient venous constriction. [source] Diet-induced obesity in Sprague,Dawley rats causes microvascular and neural dysfunctionDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2010Eric P. Davidson Abstract Background The objective of this study was to determine the effect of diet-induced obesity (DIO) on microvascular and neural function. Methods Rats were fed a standard or high fat diet for up to 32 weeks. The following measurements were carried out: vasodilation in epineurial arterioles using videomicroscopy, endoneurial blood flow using hydrogen clearance, nerve conduction velocity using electrical stimulation, size,frequency distribution of myelinated fibres of the sciatic nerve, intraepidermal nerve fibre density using confocal microscopy and thermal nociception using the Hargreaves method. Results Rats fed a high fat diet for 32 weeks developed sensory neuropathy, as indicated by slowing of sensory nerve conduction velocity and thermal hypoalgesia. Motor nerve conduction velocity and endoneurial blood flow were not impaired. Mean axonal diameter of myelinated fibres of the sciatic nerve was unchanged in high fat-fed rats compared with that in control. Intraepidermal nerve fibre density was significantly reduced in high fat-fed rats. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased and expression of neutral endopeptidase (NEP) increased in epineurial arterioles of rats fed a high fat diet. In contrast, insulin-mediated vascular relaxation was increased in epineurial arterioles. NEP activity was significantly increased in the skin of the hindpaw. Markers of oxidative stress were increased in the aorta and serum of high fat-fed rats but not in epineurial arterioles. Conclusion Chronic obesity causes microvascular and neural dysfunction. This is associated with increased expression of NEP but not oxidative stress in epineurial arterioles. NEP degrades vasoactive peptides, which may explain the decrease in microvascular function. Copyright © 2010 John Wiley & Sons, Ltd. [source] C-peptide constricts pancreatic islet arterioles in diabetic, but not normoglycaemic miceDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008Lina Nordquist Abstract Background Pancreatic islet blood flow is regulated separately from that of the exocrine pancreas, and a consistent finding during impaired glucose tolerance is an increased blood perfusion. The aim of the present study was to investigate whether C-peptide affects pancreatic islet arterioles in normal and diabetic mice. Materials and Methods Control and diabetic C57-Bl mice were studied after 2 weeks of alloxan-induced diabetes. Islet arterioles were dissected and microperfused with Dulbecco's modified Eagle medium (DMEM) solution. The effect of luminal application of mouse C-peptide was investigated. Results C-peptide reduced the diameter of islet arterioles from diabetic mice (,10 ± 4%, P < 0.05) compared to base-line values, whilst arterioles from normoglycaemic animals did not respond to C-peptide (P = 0.2). Conclusion These findings suggest a role for C-peptide in the regulation of islet blood flow, especially during conditions with impaired glucose tolerance. Copyright © 2007 John Wiley & Sons, Ltd. [source] The vasodilatory actions of insulin on resistance and terminal arterioles and their impact on muscle glucose uptakeDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2004Lucy H. Clerk Abstract Whether a discrete vascular action of insulin in skeletal muscle integrally participates in insulin-mediated glucose disposal has been extensively examined but remains a contentious issue. Here, we review some of the data both supporting and questioning the role of insulin-mediated increases in limb blood flow in glucose metabolism. We advance the hypothesis that controversy has arisen, at least in part, from a failure to recognize that insulin exerts at least three separate actions on the peripheral vasculature, each with its own characteristic dose and time responsiveness. We summarize how, viewed in this manner, certain points of contention can be resolved. We also advance the hypothesis that an action on the precapillary arteriole may play the dominant role in mediating perfusion-dependent effects of insulin on glucose metabolism in muscle. Copyright © 2003 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||