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Resistance Arteries (resistance + artery)

Distribution by Scientific Domains

Medical Sciences	87%

Kinds of Resistance Arteries

mesenteric resistance artery

penile resistance artery

Selected Abstracts

Reactive Oxygen Species Are Necessary for High Flow (Shear Stress)-induced Diameter Enlargement of Rat Resistance Arteries

MICROCIRCULATION, Issue 5 2009
ERIC J. BELIN DE CHANTEMÈLE
ABSTRACT Objectives: Chronic increases in blood flow induce remodeling associated with increases in diameter and endothelium-mediated dilation. Remodeling requires cell growth and migration, which may involve reactive oxygen species (ROS). Nevertheless, the role of ROS in flow-mediated remodeling in resistance arteries is not known. Materials and Methods: Rat mesenteric resistance arteries (MRAs) were exposed to high flow (HF) by sequentially ligating second-order MRAs in vivo. After three weeks, arteries were collected for structural, pharmacological, and biochemical analysis. Results: In HF arteries, luminal diameter (431±12 to 553±14 ,m; n=10), endothelium (acetylcholine)-mediated vasodilatation (61±6 to 77±6% relaxation) and NAD(P)H subunit (gp91phox and p67phox) expression levels, and ROS (dihydroethydine microphotography) and peroxynitrite (3-nitro-tyrosine) production were higher than in normal flow arteries. Acute ROS scavenging with tempol improved acetylcholine-dependent relaxation (92±4% relaxation), confirming that ROS are produced in HF arteries. Chronic treatment with tempol prevented the increase in diameter, reduced ROS and peroxynitrite production, and improved endothelium-mediated relaxation in HF arteries. Thus, ROS and NO were involved in HF-induced diameter enlargement, possibly through the formation of peroxynitrite, while ROS reduced the increase in endothelium-dependent relaxation. Conclusions: ROS production is necessary for flow-mediated diameter enlargement of resistance arteries. However, ROS counteract, in part, the associated improvement in endothelium-mediated relaxation. [source]

Enhanced survival of vascular smooth muscle cells accounts for heightened elastin deposition in arteries of neonatal spontaneously hypertensive rats

EXPERIMENTAL PHYSIOLOGY, Issue 4 2010
Silvia M. Arribas
Abnormal stiffening and narrowing of arteries are characteristic features of spontaneously hypertensive rats (SHR). In this strain, we have previously demonstrated an increased elastin content and abnormal organization of lamellae in conduit and resistance arteries from neonatal rats that preceded the impending inward remodelling, increased vascular stiffness and development of hypertension. The aim of this study was to assess the mechanism responsible for such excessive and aberrant elastin deposition in SHR vessels during perinatal development. We compared elastin, collagen and fibronectin production (inmunocytochemistry and quantitative assay of metabolically labelled insoluble elastin), DNA content as well as cell proliferation (proliferative cellular nuclear antigen, bromodeoxyuridine incorporation) and death rates (propidium iodide exclusion test, terminal transferase nick and labeling (TUNEL) assay) in cultures of vascular smooth muscle cells (VSMC) derived from neonatal SHR and Wistar,Kyoto (WKY) control rats. Cultures of VSMC derived from neonatal SHR exhibited hypertrophy, produced more elastin, collagen and fibronectin and contained more DNA than equally plated WKY counterparts. Further analysis revealed that the higher net DNA content in SHR-derived cultures was due to increased diploidy, but not to a heightened cell multiplication. The SHR-derived VSMC also exhibited lower rates of cell death and apoptosis, which were associated with increased levels of the anti-apoptotic protein, survivin. We therefore conclude that the peculiar heightened survival of matrix-producing VSMC in neonatal SHR is responsible for accumulation of hard-wearing elastin and other extracellular matrix elements in the growing arteries, thereby contributing to the subsequent development of systemic hypertension. [source]

Arterial Myogenic Properties of the Spontaneously Hypertensive Rat

EXPERIMENTAL PHYSIOLOGY, Issue 5 2002
Jennifer M. Hughes
When subject to a transmural pressure gradient resistance arteries develop a spontaneous, intrinsically initiated contraction which varies according to the pressure stimulus and occurs in the absence of vasoconstrictor agonists. Such pressure-dependent active changes in vascular tone are indicative of the vascular myogenic response and contribute to autoregulation and the setting of total peripheral resistance and hence blood pressure regulation. The myogenic behaviour of blood vessels provides the background tone upon which other vasomotor influences act. Hypertension is associated with a raised vascular resistance and in this article the evidence for increased myogenic activity contributing to the raised vascular resistance is reviewed. Although there are some cases that provide evidence for exaggerated myogenic responsiveness in resistance arteries taken from hypertensive animals it is not possible to conclude that enhanced myogenic contractile responses within normal pressure ranges contribute to the raised total peripheral resistance. However, the myogenic tone of the resistance arteries of the various vascular beds is subject to differing modulatory influences in hypertensive animals and their normotensive controls which may contribute to the aetiology of hypertension. [source]

Clinical methods for the evaluation of endothelial function , a focus on resistance arteries

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2006
Robinson Joannides
Abstract Endothelial dysfunction is a key event in the pathophysiology of cardiovascular diseases and appears as a strong independent predictor of cardiovascular events. In this context, biological evaluation of endothelial circulating markers can be helpful. However, functional tests using pharmacological stimuli appear more specific for the study of resistance arteries. These methods consist in the evaluation of the endothelium-dependent changes in regional vascular flow in response to local infusion of substances that act through endothelial receptors without modification of systemic arterial pressure and in comparison with a non endothelium-dependent relaxation. Flow is measured by Doppler and intravascular ultrasound in coronary circulation, laser Doppler in skin and by venous occlusion plethysmography in peripheral muscular arteries. Similar studies can be performed ex vivo using isolated resistance arteries obtained from fat subcutaneous biopsies. In addition, other information can be obtained from reactive hyperemia and the study of the flow-mediated dilatation of conduit arteries to enable a selective and comprehensive approach of the heterogeneity of endothelial function in pathophysiology. [source]

Close relation of arterial ICC-like cells to the contractile phenotype of vascular smooth muscle cell

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2007
Vladimír Pucovský
Abstract This work aimed to establish the lineage of cells similar to the interstitial cells of Cajal (ICC), the arterial ICC-like (AIL) cells, which have recently been described in resistance arteries, and to study their location in the artery wall. Segments of guinea-pig mesenteric arteries and single AIL cells freshly isolated from them were used. Confocal imaging of immunostained cells or segments and electron microscopy of artery segments were used to test for the presence and cellular localization of selected markers, and to localize AIL cells in intact artery segments. AIL cells were negative for PGP9.5, a neural marker, and for von Willebrand factor (vWF), an endothelial cell marker. They were positive for smooth muscle ,-actin and smooth muscle myosin heavy chain (SM-MHC), but expressed only a small amount of smoothelin, a marker of contractile smooth muscle cells (SMC), and of myosin light chain kinase (MLCK), a critical enzyme in the regulation of smooth muscle contraction. Cell isolation in the presence of latrunculin B, an actin polymerization inhibitor, did not cause the disappearance of AIL cells from cell suspension. The fluorescence of basal lamina protein collagen IV was comparable between the AIL cells and the vascular SMCs and the fluorescence of laminin was higher in AIL cells compared to vascular SMCs. Moreover, cells with thin processes were found in the tunica media of small resistance arteries using transmis-sion electron microscopy. The results suggest that AIL cells are immature or phenotypically modulated vascular SMCs constitutively present in resistance arteries. [source]

Reactive Oxygen Species Are Necessary for High Flow (Shear Stress)-induced Diameter Enlargement of Rat Resistance Arteries

Immunohistochemical localization of angiotensin II receptor types 1 and 2 in the mesenteric artery from spontaneously hypertensive rats

MICROSCOPY RESEARCH AND TECHNIQUE, Issue 8 2007
Carmen Diniz
Abstract Angiotensin II plays a crucial role in the control of blood pressure, acting at AT1 or AT2 receptors, and can act as a potent vasoconstrictor of the peripheral vasculature inducing hypertrophy, hyperplasia, or both, in resistance arteries. The aim of the present study was to investigate whether the pattern of distribution of angiotensin AT1 and AT2 receptors on mesenteric artery sections differs in spontaneously hypertensive rats (SHR) versus their respective controls (Wistar,Kyoto [WKY] rats). Immunohistochemistry using anti-AT1 or anti-AT2 antibodies was performed on perfused-fixed/paraffin-embedded mesenteric arteries from SHR and WKY rats. 3,3,-Diaminobenzidine tetrahydrochloride (DAB; activated by hydrogen peroxide) staining revealed distinct AT1 and AT2 labeling of all artery layers (adventitia, media and intima) from WKY rats, whereas in SHR an abundant AT1 labeling was found in both intima and adventitia and a sparser labeling in the media. There was a vast reduction of AT2 labeling throughout all layers. These results suggest a crucial role for AT2 receptors in the pathogenesis of hypertension. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. [source]

Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide Signaling

THE JOURNAL OF SEXUAL MEDICINE, Issue 8 2010
Javier Angulo PhD
ABSTRACT Introduction., Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective ,1 -adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism. Aim., We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues. Methods., Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined. Main Outcome Measures., The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses. Results., Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3 Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals. Conclusions., Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling. J Sex Med 2010;7:2681,2697. [source]

The Novel Antioxidant, AC3056 (2,6-di-t-butyl-4-((Dimethyl-4-Methoxyphenylsilyl)Methyloxy)Phenol), Reverses Erectile Dysfunction in Diabetic Rats and Improves NO-mediated Responses in Penile Tissue from Diabetic Men

THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009
Javier Angulo PhD
ABSTRACT Introduction., Diabetes is associated with a high incidence of erectile dysfunction (ED) and poor response to standard treatments. Oxidative stress could be relevant in the pathophysiology of diabetic ED. Aim., To evaluate the effects of the antioxidant, AC3056 (2,6-di- t -butyl-4-((dimethyl-4-methoxyphenylsilyl)methyloxy)phenol), on diabetic ED. Methods., Erectile responses to cavernosal nerve electrical stimulation were determined in streptozotocin-induced diabetic rats. Relaxation of human corpus cavernosal (HCC) tissue and penile resistance arteries (HPRA) from human cavernosal specimens was evaluated in organ chambers and myographs, respectively. Main Outcome Measures., The influence of AC3056 on erectile responses, lipid peroxidation, and nitrite plus nitrate serum content, and nuclear factor-,B (NF-,B) expression in penile tissue, in diabetic rats, and on endothelium-dependent and neurogenic relaxation of HCC and HPRA from diabetic patients was determined. Results., Eight weeks of diabetes caused ED in rats that was prevented by oral AC3056 (0.3% w/w in rat chow) when given from the induction of diabetes. AC3056 also prevented the diabetes-induced elevation of serum thiobarbituric acid-reactive substances (TBARS), the reduction of serum nitric oxide (NO) derivatives, and the increase of NF-,B expression. Acute oral administration of AC3056 (450 mg/kg) partially reversed ED in 8-week diabetic rats. Complete reversion of ED was achieved after 3 days of treatment with 0.3% AC3056. This effect remained after 5 weeks of treatment, but it disappeared after withdrawing for 1 week. Erectile function in diabetic rats was inversely related to serum TBARS. AC3056- (30 µM) reversed endothelial dysfunction in diabetic HCC and enhanced endothelium-dependent relaxation in diabetic HPRA and significantly potentiated neurogenic relaxation of both tissues. The reduced cGMP content in HCC from diabetic patients after exposure to acetylcholine (10 µM) was corrected by AC3056 (30 µM). Conclusions., These results suggest that oxidative stress has a relevant role in pathophysiology of diabetic ED and provide a rationale for the use of antioxidant therapy in the treatment of ED in diabetes. Angulo J, Peiró C, Cuevas P, Gabancho S, Fernández A, González-Corrochano R, La Fuente JM, Baron AD, Chen KS, and Sáenz de Tejada I. The novel antioxidant, AC3056 (2,6-di-t-butyl-4-([dimethyl-4-methoxyphenylsilyl] methyloxy) phenol), reverses erectile dysfunction in diabetic rats and improves NO-mediated responses in penile tissue from diabetic men. J Sex Med 2009;6:373,387. [source]

Desensitization of endothelial P2Y1 receptors by PKC-dependent mechanisms in pressurized rat small mesenteric arteries

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2009
R Rodríguez-Rodríguez
Background and purpose:, Extracellular nucleotides play a crucial role in the regulation of vascular tone and blood flow. Stimulation of endothelial cell P2Y1 receptors evokes concentration-dependent full dilatation of resistance arteries. However, this GPCR can desensitize upon prolonged exposure to the agonist. Our aim was to determine the extent and nature of P2Y1 desensitization in isolated and pressurized rat small mesenteric arteries. Experimental approach:, The non-hydrolyzable selective P2Y1 agonist ADP,S (3 µM) was perfused through the lumen of arteries pressurized to 70 mmHg. Changes in arterial diameter and endothelial cell [Ca2+]i were obtained in the presence and absence of inhibitors of protein kinase C (PKC). Key results:, ADP,S evoked rapid dilatation to the maximum arterial diameter but faded over time to a much-reduced plateau closer to 35% dilatation. This appeared to be due to desensitization of the P2Y1 receptor, as subsequent endothelium-dependent dilatation to acetylcholine (1 µM) remained unaffected. Luminal treatment with the PKC inhibitors BIS-I (1 µM) or BIS-VIII (1 µM) tended to augment concentration-dependent dilatation to ADP,S (0.1,3 µM) and prevented desensitization. Another PKC inhibitor, Gö 6976 (1 µM), was less effective in preventing desensitization. Measurements of endothelial cell [Ca2+]i in pressurized arteries confirmed the P2Y1 receptor but not M3 muscarinic receptor desensitization. Conclusions and implications:, These data demonstrate for the first time the involvement of PKC in the desensitization of endothelial P2Y1 receptors in pressurized rat mesenteric arteries, which may have important implications in the control of blood flow by circulating nucleotides. [source]

Calcium dobesilate potentiates endothelium-derived hyperpolarizing factor-mediated relaxation of human penile resistance arteries

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003
Javier Angulo
We have evaluated the participation of endothelium-derived hyperpolarizing factor (EDHF) in the endothelium-dependent relaxation of isolated human penile resistance arteries (HPRA) and human corpus cavernosum (HCC) strips. In addition, the effect of the angioprotective agent, calcium dobesilate (DOBE), on the endothelium-dependent relaxation of these tissues was investigated. Combined inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) nearly abolished the endothelium-dependent relaxation to acetylcholine (ACh) in HCC, while 60% relaxation of HPRA was observed under these conditions. Endothelium-dependent relaxation of HPRA resistant to NOS and COX inhibition was prevented by raising the extracellular concentration of K+ (35 mM) or by blocking Ca2+ -activated K+ channels, with apamin (APA; 100 nM) and charybdotoxin (CTX; 100 nM), suggesting the involvement of EDHF in these responses. Endothelium-dependent relaxation to ACh was markedly enhanced by DOBE (10 ,M) in HPRA but not in HCC. The potentiating effects of DOBE on ACh-induced responses in HPRA, remained after NOS and COX inhibition, were reduced by inhibition of cytochrome P450 oxygenase with miconazole (0.3 mM) and were abolished by high K+ or a combination of APA and CTX. In vivo, DOBE (10 mg kg,1 i.v.) significantly potentiated the erectile responses to cavernosal nerve stimulation in male rats. EDHF plays an important role in the endothelium-dependent relaxation of HPRA but not in HCC. DOBE significantly improves endothelium-dependent relaxation of HPRA mediated by EDHF and potentiates erectile responses in vivo. Thus, EDHF becomes a new therapeutic target for the treatment of erectile dysfunction (ED) and DOBE could be considered a candidate for oral therapy for ED. British Journal of Pharmacology (2003) 139, 854,862. doi:10.1038/sj.bjp.0705293 [source]

Involvement of H2O2 in superoxide-dismutase-induced enhancement of endothelium-dependent relaxation in rabbit mesenteric resistance artery

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2003
Takeo Itoh
The mechanism underlying the enhancement by superoxide dismutase (SOD) of endothelium-dependent relaxation was investigated in rabbit mesenteric resistance arteries. SOD (200 U ml,1) increased the production of H2O2 in smooth muscle cells (as indicated by the use of an H2O2 -sensitive fluorescent dye). Neither SOD nor catalase (400 U ml,1) modified either the resting membrane potential or the hyperpolarization induced by acetylcholine (ACh, 1 ,M) in smooth muscle cells. In arteries constricted with noradrenaline, the endothelium-dependent relaxation induced by ACh (0.01,1 ,M) was enhanced by SOD (200 U ml,1) (P<0.01). This action of SOD was inhibited by L - NG -nitroarginine (nitric oxide (NO)-synthase inhibitor) but not by either charybdotoxin+apamin (Ca2+ -activated-K+ -channel blockers) or diclofenac (cyclooxygenase inhibitor). Neither ascorbate (50 ,M) nor tiron (0.3 mM), superoxide scavengers, had any effect on the ACh-induced relaxation, but each attenuated the enhancing effect of SOD on the ACh-induced relaxation. Similarly, catalase (400 U ml,1) inhibited the effect of SOD without changing the ACh-induced relaxation. In endothelium-denuded strips constricted with noradrenaline, SOD enhanced the relaxation induced by the NO donor 1-hydroxy-2-oxo-3-(N -methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7) (P<0.05). Ascorbate and catalase each attenuated this effect of SOD. H2O2 (1 ,M) enhanced the relaxation on the noradrenaline contraction induced by NOC-7 and that induced by 8-bromo-cGMP, a membrane-permeable analogue of guanosine 3,,5, cyclic monophosphate (cGMP). SOD had no effect on cGMP production, whether measured in endothelium-intact strips following an application of ACh (0.1 ,M) or in endothelium-denuded strips following an application of NOC-7 (0.1 ,M). It is suggested that in rabbit mesenteric resistance arteries, SOD increases the ACh-induced, endothelium-dependent relaxation by enhancing the action of NO in the smooth muscle via its H2O2 -producing action (rather than via a superoxide-scavenging action). British Journal of Pharmacology (2003) 139, 444,456. doi:10.1038/sj.bjp.0705255 [source]

Redox-dependent signalling by angiotensin II and vascular remodelling in hypertension

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2003
Rhian M Touyz
Summary 1.,Hypertension is associated with structural alterations of resistance arteries, a process known as remodelling (increased media-to-lumen ratio). 2.,At the cellular level, vascular remodelling involves changes in vascular smooth muscle cell (VSMC) growth, cell migration, inflammation and fibrosis. These processes are mediated via multiple factors, of which angiotensin (Ang) II appears to be one of the most important in hypertension. 3.,Angiotensin II signalling, via AT1 receptors, is upregulated in VSMC from resistance arteries of hypertensive patients and rats. This is associated with hyperactivation of vascular NADPH oxidase, leading to increased generation of reactive oxygen species (ROS), particularly O2, and H2O2. 4.,Reactive oxygen species function as important intracellular second messengers to activate many downstream signalling molecules, such as mitogen-activated protein kinase, protein tyrosine phosphatases, protein tyrosine kinases and transcription factors. Activation of these signalling cascades leads to VSMC growth and migration, modulation of endothelial function, expression of pro-inflammatory mediators and modification of extracellular matrix. 5.,Furthermore, ROS increase intracellular free Ca2+ concentration ([Ca2+]i), a major determinant of vascular reactivity. 6.,All these processes play major roles in vascular injury associated with hypertension. Accordingly, ROS and the signalling pathways that they modulate provide new targets to regress vascular remodelling, reduce peripheral resistance and prevent hypertensive end-organ damage. 7.,In the present review, we discuss the role of ROS as second messengers in AngII signalling and focus on the implications of these events in the processes underlying vascular remodelling in hypertension. [source]

Fluvastatin remodels resistance arteries in genetically hypertensive rats, even in the absence of any effect on blood pressure

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2002
Janet M Ledingham
Summary 1.,The aims of the present study were, first, to determine whether, in the genetically hypertensive (GH) rat, fluvastatin would lower blood pressure and remodel mesenteric resistance arteries (MRA) and the basilar artery and, second, to see whether treatment with a combination of fluvastatin and the angiotensin receptor antagonist valsartan would have any extra beneficial effect on blood pressure and vascular remodelling. 2.,Male GH rats had tail-cuff systolic blood pressure (SBP) monitored weekly from the age of 7 to 12 weeks. Groups (n = 12,14) were treated with fluvastatin (4 mg/kg per day), valsartan (5 mg/kg per day), both mixed in with chow, or a combination of fluvastatin 4 mg/kg per day + valsartan 5 mg/kg per day. Untreated GH and a group of normotensive Wistar (N) rats served as control groups. 3.,At 12 weeks of age, intra-arterial (i.a.) blood pressure was measured by femoral cannulation and rats were then perfused (at the SBP of the animal) with Tyrode's solution containing heparin and papaverine followed by 2.5% glutaraldehyde in Tyrode's solution; MRA and basilar arteries were embedded in Technovit. Serial sections were cut and Giemsa stained and stereological methods used to obtain media width, lumen diameter, medial cross-sectional area (CSA) and the ratio of media width to lumen diameter. Hearts were weighed to determine left ventricular (LV) mass. 4.,Fluvastatin had no effect on blood pressure or LV mass, whereas valsartan given alone or with fluvastatin significantly reduced both parameters. 5.,In MRA, fluvastatin reduced medial CSA, increased lumen size and, therefore, probably decreased vascular resistance. The media/lumen ratio was reduced to a level below that seen with the combination treatment and to below that of the N group. 6.,In the basilar artery, fluvastatin and valsartan showed similar outward remodelling of the lumen and reduction in the media/lumen ratio. The combination treatment group showed, in addition, a reduction in medial CSA and an even lower ratio than the GH group on fluvastatin or valsartan alone or the N group. 7.,Although fluvastatin has no effect on blood pressure, it does cause significant remodelling of MRA and the basilar artery. These beneficial structural changes in a peripheral resistance artery bed and in an artery involved in regulating resistance in the brain are worthy of further study. [source]

Effects Of Nitric Oxide Synthase Inhibition And Low-Salt Diet On Blood Pressure And Mesenteric Resistance Artery Remodelling In Genetically Hypertensive Rats

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2001
Janet M Ledingham
SUMMARY 1. Nitric oxide synthase (NOS)-inhibited genetically hypertensive (GH) rats on normal and low-sodium diets were additionally given valsartan or felodipine to establish whether low-Na intake would have extra beneficial effects on blood pressure and cardiovascular structure. 2. Male GH rats on normal or low-Na diets were treated with the NOS inhibitor NG -nitro- L -arginine methyl ester (L -NAME) from the age of 7 to 12 weeks and were given either valsartan (10 mg/kg per day) or felodipine (30 mg/kg per day). 3. Systolic blood pressure (SBP; tail-cuff) was measured weekly. At 12 weeks of age, mesenteric resistance arteries (MRA) were fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained. Stereological analysis was used to obtain MRA media width, lumen diameter, ratio of media width/lumen diameter (M/L) and medial cross-sectional area (CSA). Left ventricular (LV) mass was determined. 4. In GH L -NAME-treated rats on a normal diet, SBP was significantly reduced (P < 0.001) by valsartan and felodipine, as was LV mass (valsartan P < 0.001; felodipine P < 0.05). A low-Na diet with valsartan caused a further fall in SBP (P < 0.01) but, with felodipine, SBP increased in rats on a low-Na diet (P < 0.05). 5. Valsartan with the low-Na diet had no further effect on LV mass, but the felodipine-treated group on a low-Na diet had a lower LV mass (P < 0.05) than rats on a normal diet. 6. In MRA from the GH L -NAME + valsartan-treated group, there was hypotrophic inward remodelling; the M/L ratio was reduced (P < 0.001) compared with GH L -NAME-treated rats. The lumen was outwardly remodelled in the group on the low-Na diet. 7. The GH L -NAME + felodipine-treated group showed hypotrophic outward remodelling and a reduction in M/L ratio compared with the GH L -NAME-treated group (P < 0.001). A low-Na diet had no further effect on MRA. 8. A low-Na diet + valsartan had beneficial effects on SBP and MRA, where outward remodelling of the lumen occurred and, thus, resistance was reduced. In contrast, felodipine with a low-Na diet increased SBP, reduced LV mass and had no effect on MRA structure. Valsartan treatment with a low-Na diet confers extra benefits on blood pressure and MRA structure. [source]