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Spontaneously Hypertensive Rats (spontaneously + hypertensive_rat)
Selected AbstractsArterial Myogenic Properties of the Spontaneously Hypertensive RatEXPERIMENTAL PHYSIOLOGY, Issue 5 2002Jennifer 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] Microvascular Display of Xanthine Oxidase and NADPH Oxidase in the Spontaneously Hypertensive RatMICROCIRCULATION, Issue 7 2006FRANK A. DELANO ABSTRACT Objective: Oxygen free radical production in hypertension may be associated with elevated arteriolar tone and organ injury. Previous results suggest an enhanced level of oxygen free radical formation in microvascular endothelium and in circulating neutrophils associated with xanthine oxidase activity in the spontaneously hypertensive rats (SHR) compared with their normotensive controls, the Wistar Kyoto rats (WKY). The aim of this study was to gain more detailed understanding of where oxidative enzymes are located in the microcirculation. Methods: An approach was developed to delineate the cellular distribution of two selected oxidative enzymes, xanthine oxidase and nicotinamide adenine dinucleotide phosphate (NADPH) dependent oxidase (protein 67-kDa fraction). Immunolabeling with peroxidase substrate was utilized, which permits full delineation of the primary antibody in all microvascular structures of the mesentery. Results: Xanthine oxidase is present in the endothelium of all segments of the microcirculation, in mast cells, and in parenchymal cells of the mesentery. NADPH oxidase can be detected in the endothelium, leukocytes, and mast cells and with lower levels in parenchymal cells. The mesentery of WKY and SHR has similar enzyme distributions with enhancements on the arteriolar and venular side of the microcirculation that coincide with the sites of enhanced free radical production recently reported. Immune label measurements under standardized conditions indicate that both enzymes are significantly enhanced in the SHR. Adrenalectomy, which serves to reduce the blood pressure and free radical production of the SHR to normotensive levels, leads to a reduction of NADPH and xanthine oxidase to normotensive levels, while supplementation of adrenalectomized SHR with dexamethasone significantly increases the oxidase expression in several parts of the microcirculation to levels above the WKY rats. Conclusion: The results indicate that enhanced expression of NADPH and xanthine oxidase in the SHR depends on an adrenal pathway that is detectable in the arteriolar and venular network at high and low pressure regions of the circulation. [source] Rosuvastatin Attenuates Heart Failure and Cardiac Remodelling in the Ageing Spontaneously Hypertensive RatBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009David Loch The ageing spontaneously hypertensive rat (SHR) closely mimics the chronic heart failure disease process observed in humans. This study examined the structural and functional changes in the cardiovascular system of 15-month-old SHR and normotensive Wistar-Kyoto (WKY) rats treated with rosuvastatin (20 mg/kg/day perorally) for 24 weeks. Cardiovascular structure and function were monitored serially by echocardiography. At 21 months, ex vivo Langendorff, electrophysiological or histological studies were performed. Chronic rosuvastatin treatment attenuated elevations of left ventricular wet weight (mg/g body weight: 21-month WKY, 2.30 ± 0.04; 15-month SHR, 3.03 ± 0.08; 21-month SHR, 4.09 ± 0.10; 21-month SHR + rosuvastatin, 3.50 ± 0.13), myocardial extracellular matrix content (% left ventricular area: 21-month WKY, 7.6 ± 0.5; 15-month SHR, 13.2 ± 0.8; 21-month SHR 19.6 ± 1.0; 21-month SHR with rosuvastatin 14.6 ± 1.2) and diastolic stiffness (,: 21-month WKY, 24.9 ± 0.6; 15-month SHR, 26.4 ± 0.4; 21-month SHR, 33.1 ± 0.8; 21-month SHR + rosuvastatin, 27.5 ± 0.6) as well as attenuating the deterioration of systolic and diastolic function (fractional shortening %: 21-month WKY, 66 ± 2; 15-month SHR, 51 ± 3; 21-month SHR, 38 ± 3; 21-month SHR + rosuvastatin, 52 ± 4). There was no effect on the increased systolic blood pressure, plasma low-density lipoprotein concentrations or the prolonged action potential duration. Thus, chronic rosuvastatin treatment may attenuate myocardial dysfunction in heart failure by preventing fibrosis. [source] Antihypertensive Activities of Peptides Derived from Porcine Skeletal Muscle Myosin in Spontaneously Hypertensive RatsJOURNAL OF FOOD SCIENCE, Issue 1 2002Y. Nakashima ABSTRACT: Antihypertensive activities derived from porcine skeletal muscle proteins were investigated. Thermolysin hydrolysates of porcine muscle water-insoluble proteins demonstrated antihypertensive activities in spontaneously hypertensive rats when administrated in single oral doses. Hydrolysates of porcine myosin and peptides (Met-Asn-Pro-Pro-Lys, Ile-Thr-Thr-Asn-Pro, Met-Asn-Pro, Pro-Pro-Lys) with parts of the sequence of myosin showed antihypertensive activities. This is the first report of antihypertensive activities of peptides derived from muscle proteins of domestic animals. The hydrolysates of porcine muscle protein and their corresponding bioactive peptides might be utilized for physiologically functional foods. [source] Direct Evidence for Imidazoline (I1) Receptor Modulation of Ethanol Action on Norepinephrine-Containing Neurons in the Rostral Ventrolateral Medulla in Conscious Spontaneously Hypertensive RatsALCOHOLISM, Issue 4 2007Guichu Li Background: Enhancement of the rostral ventrolateral medulla (RVLM) presympathetic (norepinephrine, NE) neuronal activity represents a neurochemical mechanism for the pressor effect of ethanol. In this study, we tested the hypothesis that ethanol action on RVLM presympathetic neurons is selectively influenced by the signaling of the local imidazoline (I1) receptor. To support a neuroanatomical and an I1 -signaling selectivity of ethanol, and to circumvent the confounding effects of anesthesia, the dose-related neurochemical and blood pressure effects of ethanol were investigated in the presence of selective pharmacological interventions that cause reduction in the activity of RVLM or nucleus tractus solitarius (NTS) NE neurons via local activation of the I1 or the ,2 -adrenergic receptor in conscious spontaneously hypertensive rats. Results: Local activation of the I1 receptor by rilmenidine (40 nmol) or by the I1/,2 receptor mixed agonist clonidine (1 nmol), and local activation of the ,2 -adrenergic receptor (,2AR) by the pure ,2AR agonist , -methylnorepinephrine (, -MNE, 10 nmol) caused reductions in RVLM NE, and blood pressure. Intra-RVLM ethanol (1, 5, or 10 ,g), microinjected at the nadir of the neurochemical and hypotensive responses, elicited dose-dependent increments in RVLM NE and blood pressure in the presence of local I1,but not ,2 -receptor activation. Only intra-NTS , -MNE, but not rilmenidine or clonidine, elicited reductions in local NE and blood pressure; ethanol failed to elicit any neurochemical or blood pressure responses in the presence of local activation of the ,2AR within the NTS. Conclusion: The findings support the neuroanatomical selectivity of ethanol, and support the hypothesis that the neurochemical (RVLM NE), and the subsequent cardiovascular, effects of ethanol are selectively modulated by I1 receptor signaling in the RVLM. [source] ORIGINAL RESEARCH,BASIC SCIENCE: Effects of ACE Inhibition and Beta-Blockade on Female Genital Structures in Spontaneously Hypertensive RatsTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2007Jorge E. Toblli MD ABSTRACT Introduction and Aim., This study evaluated the possible differences between an angiotensin converting enzyme (ACE) inhibitor and a beta-blocker concerning their potential protective role on female external genitalia in spontaneously hypertensive rats (SHR). Main Outcome Measures., Morphological changes in the clitoris after antihypertensive treatments. Methods., For 6 months, SHR received no treatment; SHR + ramipril (RAM), SHR + atenolol (AT), and control Wistar Kyoto (WKY) rats received no treatment. Clitorises were processed for immunohistochemistry using anti-,-smooth muscle actin (,-SMA), anti-collagen I and III, anti-transforming growth factor ,1 (TGF,1), and anti-endothelial nitric oxide synthase (eNOS) antibodies. Results., SHR + RAM and SHR + AT presented significantly lower blood pressure in both groups vs. untreated SHR. Compared with WKY, ,-SMA was increased in the arteries and in the cavernous spaces of the clitoris together with a marked increase in wall/lumen ratio in clitoral vessels in untreated SHR. All these alterations were diminished in SHR + AT (P < 0.01). SHR + RAM presented differences with respect to SHR + AT in the reduction of these variables. TGF,1 expression in the vessel wall from the clitoris and collagen I and III deposition in the interstitium from the clitoris in untreated SHR were significantly more (P < 0.01) than in WKY. While SHR + AT showed a mild decrease in these variables, SHR + RAM presented a significant reduction (P < 0.01) in TGF,1 expression interstitial fibrosis and in both types of collagens. Positive immunostaining of eNOS in the sinusoidal endothelium from the clitoris was less (P < 0.01) in untreated SHR (3.4 ± 1.3%) and SHR + AT (5.1 ± 1.2%) than in SHR + RAM (17.2 ± 1.6%) and WKY (15.9 ± 1.7%). Untreated SHR and SHR + AT presented more surrounding connective tissue at the perineurium in the clitoris (P < 0.01) than SHR + RAM. Conclusion., ACE inhibition provided a considerable protective role on the female external genitalia structures in SHR by a mechanism that may be, at least in part, independent of the degree of blood pressure lowering. Toblli JE, Cao G, Casabé AR, and Bechara AJ. Effects of ACE inhibition and beta-blockade on female genital structures in spontaneously hypertensive rats. J Sex Med 2007;4:1593,1603. [source] Altered Mitogen-Activated Protein Kinase Activation In Vascular Smooth Muscle Cells From Spontaneously Hypertensive RatsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2002Takao Kubo SUMMARY 1.,We previously reported that activation function of mitogen-activated protein kinases (MAPK) is enhanced in aorta strips from both prehypertensive and hypertensive spontaneously hypertensive rats (SHR) and that this enhancement of MAPK activation results from enhanced MAPK activation reactivity to angiotensin (Ang) II in SHR aorta strips. 2.,The purpose of the present study was to examine whether the enhanced function of the vascular angiotensin system observed in SHR aorta strips results from genetic alterations of vascular smooth muscle cells from SHR. 3.,Basal MAPK activity was within normal limits in cells from 4-week-old SHR, whereas enzyme activity was enhanced in 9-week-old SHR compared with age-matched Wistar-Kyoto (WKY) rats. 4.,Mitogen-activated protein kinase activation reactivity to AngII and endothelin-1 was enhanced in 9-week-old SHR cells but not in 4-week-old SHR cells. The enhancement of basal MAPK activity in 9-week-old SHR cells was abolished by a combination of the angiotensin AT1 receptor antagonist losartan and the endothelin receptor antagonist BQ123. 5.,These findings suggest that MAPK activation function in 4-week-old SHR cells is not enhanced. Thus, it appears that factors outside vascular smooth muscle cells are needed for the enhanced MAPK activation observed in 4-week-old SHR aorta strips. In 9-week-old SHR, MAPK activation function is enhanced in cells themselves and this function may, at least in part, contribute to the enhanced MAPK activation observed in SHR aorta strips. [source] Impaired Heart Function And Noradrenaline Release After Ischaemia In Stroke-Prone Spontaneously Hypertensive RatsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2000Hong Chen SUMMARY 1. Stroke-prone spontaneously hypertensive rats (SHRSP) are a strain of rat that exhibit severely high blood pressure and stroke attacks at an early age, but their heart function in vitro has seldom been studied in detail. Although the activity of the sympathetic nervous system is known to increase after myocardial ischaemia, there is little information about the cardiac release of noradrenaline (NA) associated with heart function after ischaemia in SHRSP. The aim of the present study was to examine heart function and cardiac NA release after ischaemia in SHRSP. 2. Isolated hearts of 4- and 8-month-old SHRSP and age-matched Wistar-Kyoto (WKY) rats were perfused in a working heart preparation and were subjected to 30 min ischaemia followed by 30 min reperfusion. Heart function and coronary flow were monitored throughout the experiment. Coronary effluent was collected for determination of NA using high- performance liquid chromatography coupled with electrochemical detection. 3. Under baseline conditions, cardiac output of 4-month-old SHRSP was slightly but significantly decreased compared with that of WKY rats (P < 0.05), although coronary flow was maintained normally at this age. Eight-month-old SHRSP showed a further impairment of systolic heart function, with lower coronary flow and higher coronary vascular resistance under baseline conditions. Elevated left ventricular end-diastolic pressure was evident in SHRSP at both ages before ischaemia. Heart function was severely damaged after 30 min global ischaemia in SHRSP from both age groups. Stroke-prone spontaneously hypertensive rats also showed lower coronary flow and higher coronary vascular resistance during reperfusion. 4. Coronary NA was not detectable in WKY rats or SHRSP at 4 months of age under baseline conditions. In 8-month-old SHRSP, pre-ischaemic NA release was significantly higher than that in age-matched WKY rat controls. The concentration of NA in the coronary effluent of SHRSP during reperfusion was also significantly higher than that of WKY rats at both ages. 5. These data demonstrate that SHRSP have early impairment of both systolic and diastolic heart function compared with WKY rats. Severe damage of heart function and coronary flow after ischaemia in SHRSP was accompanied with an increased release of NA, which may play a harmful role in heart function impairment in SHRSP after ischaemia. [source] Acute And Chronic Sympathoinhibition On Carotid Artery Diameter Of Spontaneously Hypertensive Rats: Effects Of Clonidine And FlesinoxanCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2000H Dabiré SUMMARY 1. Hypertensive conduit arteries are thicker and stiffer than those of normotensive controls. Whether they are specifically sensitive to central sympathoinhibition has never been investigated. 2. The effects of acute (24 h infusion) and chronic (4 week infusion) treatments with clonidine (0.01 and 0.1 mg/kg per day) and flesinoxan (1 and 3 mg/kg per day) on carotid artery diameter were investigated in spontaneously hypertensive rats. At the end of treatment, blood pressure (BP) was recorded in the rats while they were conscious. Rats were then anaesthetized for carotid artery diameter measurements using an ultrasonic echo-tracking device. 3. In conscious rats, clonidine significantly decreased BP and heart rate (HR) following acute but not chronic treatment. In contrast, flesinoxan significantly decreased BP following both the acute and chronic treatment. In anaesthetized animals, the two agents have opposite effects on isobaric carotid artery diameter, with a decrease under clonidine and an increase under flesinoxan. After 4 weeks infusion, the reactivity of aortic rings was studied in organ chambers. Flesinoxan, but not clonidine, caused the relaxation of potassium chloride precontracted aortic segments. 4. The results indicate that although clonidine and flesinoxan are centrally acting antihypertensive agents, the drug-induced changes in isobaric carotid diameter may be influenced by local factors independent of the central action of the two drugs. [source] Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidantsACTA PHYSIOLOGICA, Issue 4 2007M. P. Koeners Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source] | |||||||||||||