Arterial hypertension, myocardial hypertrophy and disorders of cardiac rhythm induced by ligation of the left coronary artery in the rat

Cardiac hypertrophy and hypertension are major elements in sudden cardiac death in patients with coronary artery disease. To investigate in animals the hypothesis that left ventricular hypertrophy (LVH) and/or hypertension increase the incidence of severe ventricular arrhythmias, we have undertaken a 30 min period of coronary artery ligation in anaesthetized spontaneously hypertensive rats (SHR), normotensive (NT) Wistar Kyoto (WKY) and Wistar (W) rats. Mean systolic blood pressure (SBP) was 190 +/- 4 mmHg in SHR vs 123 +/- 5 mmHg in WKY and 116 +/- 4 mmHg in W (p less than 0.001). LVH index was 2.81 +/- 0.04 in SHR vs 196 +/- 0.03 in WKY and 1.65 +/- 0.05 in W (p less than 0.01). Incidence (IVF) and duration (DVF) of ventricular fibrillation were significantly more elevated in SHR than in NT rats. IVF was 100 p. 100 in SHR vs 36 p. 100 in WKY and 27 p. 100 in W (p less than 0.001); DVF was 61 +/- 17 s in SHR vs 6 +/- 6 s in WKY and W (p less than 0.001). In addition the calcium channel blocker nicardipine (N) has been administered orally to SHR either chronically during eight weeks (20 mg/kg-1 per os twice daily) or acutely as a single dose of 20 mg/kg. After long term treatment (LT) with N the LVH index and SBP were significantly reduced when compared to vehicle treated (VT) SHR; whereas a single administration of N (AT) only decreased SBP without affecting LVH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular oxidative stress precedes high blood pressure in spontaneously hypertensive rats

This study examines whether longitudinal antioxidant treatment initiated in prehypertensive spontaneously hypertensive rats (SHR) can attenuate vascular oxidant stress and prevent blood pressure elevation during development. Male SHR and age-matched Wistar-Kyoto rats (WKY) were treated from 6 to 11 weeks of age with Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl) (1 mmol/l in drinking water), a membrane-permeable superoxide dismutase mimetic. Mean systolic blood pressures (SBPs) were measured by tail-cuff Agonist-induced and basal O2- production was measured in thoracic aortas of 6- and 11-week-old SHR and WKY by lucigenin-derived chemiluminescence and oxidative fluorescent microscopy, respectively. SBP of 6-week-old SHR (131 +/- 5 mmHg) and WKY (130 +/- 4 mmHg) were not different; however, 11-week-old SHR SBP (171 +/- 4 mmHg) was significantly greater (p = .0001) than 11-week-old WKY SBP (143 +/- 5 mmHg). Tempol treatment completely, but reversibly, prevented this age-related rise in SHR SBP (SHR + Tempol: 137 +/- 4 mmHg; p < .0001 versus untreated SHR). Agonist-induced vascular O2- was increased in 6- (p = .03) and 11-week-old SHR (p < .0001) and 11-week-old WKY (p = .03) but not in 6-week-old WKY. Long-term Tempol treatment significantly lowered O2- production in both strains. Basal O2- measurements in both 6- and 11-week-old SHR were qualitatively increased compared with age-matched WKY; this increase in SHR was inhibited with in vitro Tempol treatment. These data show that antioxidant treatment to reduce oxidative stress prevents the age-related development of high blood pressure in an animal model of genetic hypertension.     

Urinary kallikrein activity in conscious spontaneously-hypertensive rats: development as a function of age

Urinary excretion of active kallikrein was determined every day (amidolytic assay) in 6 male Okamoto-Aoki spontaneously hypertensive rats (SHR) and in 6 male normotensive Wistar-Kyoto rats (WKY) from ages 3 to 6 weeks and from 12 to 16 weeks. The rats were placed into individual metabolic cages and allowed free access to food having normal sodium content and to tap water. Urinary kallikrein excretion (UKall V, nKat/24 h) was lower in 3-week-old SHR (7.8 +/- 1.4 nKat/24 h) than in WKY (15.5 +/- 2.3 nKat/24 h, p less than 0.01) at a moment when systolic blood pressure (BP) in SHR (85.5 +/- 4.0 mmHg) was already higher than in WKY (76.3 +/- 4.6 mmHg, p less than 0.01). The slope of the increase in kallikrein excretion from week 3 to week 6 was not different for SHR and WKY (y = 6.39 x - 12.09, r = 0.95 vs y = 7.49 x - 9.40, r = 0.93). In contrast, from week 12 to week 15, this slope was slightly negative for SHR (y = 1.08 x + 59.38, r = 0.66) and became significantly different (p less than 0.05) from the slope in WKY which remained positive (y = 5.09 x + 7.05, r = 0.48). The relation between kallikrein excretion and systolic BP was an exponential curve for both SHR and WKY. But the curve of SHR (y = 1.22.e0.03x, r = 0.91) was significantly different (p less than 0.01) from the curve of WKY (y = 1.08.e0.03x, r = 0.95). For each identical systolic BP, UKall V was always lower in SHR than in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renomedullary interstitial cell lipid droplet content is increased in spontaneously hypertensive rats and by low salt diet.

OBJECTIVE: To compare the volumes of renomedullary interstitial cell (RMIC) lipid droplets (putative source of vasodepressor substance) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats on high and low salt diets as an indication of whether the renomedullary vasodepressor system of the SHR is defective. METHODS: Ten-week-old male SHR and WKY rats received a low (0.05% w/w) or high salt (5.0%) diet for 21 days. Conscious mean arterial pressure (MAP) was measured and the renal papilla perfusion fixed with a high osmolarity fixative. Using electron microscopic stereological techniques, the volume density of lipid in RMIC (VVLipid,RMIC) and the total volumes of lipid (VLipid) and RMIC (VRMIC) in papilla were measured. RESULTS: MAP of SHR (high 155 +/- 3 mmHg; low 151 +/- 3 mmHg) was significantly greater than WKY rats (high 126 +/- 2 mmHg; low 129 +/- 2 mmHg; P< 0.001), however salt diet had no significant effect on MAP. The VLipid of rats on the low salt diet was approximately 2.5 times greater than in rats on the high salt diet (P < 0.01). SHR had significantly greater VLipid than WKY rats irrespective of salt diet (P< 0.05; SHR-low 0.245 +/- 0.031 mm3, SHR-high 0.093 +/- 0.007 mm3; WKY-low 0.126 +/- 0.032 mm3, WKY-high 0.051 +/- 0.020 mm3). Similar differences were seen for VVLipid,RMIC, however VRMIC was not different between rat strains or salt diet groups. CONCLUSIONS: SHR and WKY rats responded similarly to the altered salt diets, and SHR demonstrated greater volumes of stored RMIC lipid droplets irrespective of the level of salt intake. These results indicate that SHR hypertension is not due to a deficiency in the amount of lipid droplets, the putative source of the renomedullary vasodepressor substance and that the renomedullary vasodepressor system of the SHR is capable of responding normally to the physiological stimulus of altered salt intake.     

The effects of single and combined application of ramipril and losartan on renal structure and function in hypertensive rats

The objective of the present study was to investigate the effects of single and combined administration of ramipril and losartan on renal structure and function in spontaneously hypertensive rats (SHRs). Thirty-two 9-week-old SHRs and eight Wistar-Kyoto (WKY) rats were randomly divided into five groups: the WKY control group, the SHR control group, the SHR-ramipril group, the SHR-losartan group, and the SHR-combined mediation group. The rat body weight, SBP, heart rate, and urinary albumin excretion rate (UAER) were measured. (1) The SBP was reduced to the normal level in all groups of rats except for the SHR control group. Combined administration of ramipril and losartan can be reduced to the normal level earlier than single (P < 0.01). (2) The SHR-ramipril group and the SHR-losartan group still experienced a higher UAER than that in the WKY control group (P < 0.01). (3) The renal mass/BW ratio was decreased in the SHR-ramipril group, SHR-losartan group, and SHR-combined medication group compared to that in the SHR control group (P < 0.01). (4) Compared with the SHR control group, the SHR-ramipril group, the SHR-losartan group, and the SHR-combined medication group had a lower percentage of the IOD of glomerular collagen relative to the glomerular area (P < 0.01). (5) The reduction in tubulointerstitial injury score was more significant in the SHR-combined medication group than in the SHR-ramipril group and the SHR-losartan group (P < 0.01). The combination of ramipril and losartan is superior to either single drug in reducing the UAER, resisting glomerular collagen deposition, and protecting renal tubular structure.     

Modulation of nitric oxide synthase activity in brain, liver, and blood vessels of spontaneously hypertensive rats by ascorbic acid: protection from free radical injury

End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 +/- 7 mmHg and 142 +/- 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 +/- 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 +/- 0.02, 0.14 +/- 0.003, and 1.54 +/- 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 +/- 1%, 21 +/- 3%, and 44 +/- 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 +/-.03, 0.11 +/-.01, and 0.87 +/-.08 pmol citruline/mg protein to 0.93 +/- 0.01, 0.13 +/- 0.001, and 1.11 +/- 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 +/- 0.06, 0.11 +/- 0.005, and 0.47 +/- 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 +/- 3%, 64 +/- 3%, and 104 +/- 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 +/- 1% and 34 +/- 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 +/- 0.1%; p < 0.05), nitrite (53 +/- 2%; p < 0.05) and superoxide dismutase (SOD) activity (36 +/- 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be protected by antioxidant, which improves total antioxidant status, and SOD thus may prevent high blood pressure and its complications.     

Role of oxidative stress in the sex differences in blood pressure in spontaneously hypertensive rats

OBJECTIVE: The hypothesis was tested that differences in oxidative stress play a role in the sex differences in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male and female SHR [and Wistar-Kyoto (WKY) rats in the long-term study] (n = 6-12 per group) received tempol (30 mg/kg per day) or tap water for 6 weeks from 9 to 15 weeks of age or from birth until 15 weeks of age. Blood pressure [mean arterial pressure (MAP)] and kidney tissue F2-isoprostane (IsoP) were measured at 15 weeks of age. RESULTS: In SHR given tempol for 6 weeks, blood pressure and IsoP were reduced in males, but not in females. In SHR given tempol from birth, MAP was higher in SHR than WKY rats (SHR males, 181 +/- 2 mmHg; SHR females, 172 +/- 3 mmHg; WKY males, 100 +/- 2 mmHg; WKY females, 101 +/- 2 mmHg, P < 0.01), and tempol reduced MAP by 14% (156 +/- 3) and 26% (127 +/- 4) in male and female SHR, respectively, but had no effect on WKY rats. IsoP was higher in SHR than WKY rats and higher in male SHR than female SHR (SHR males, 5.18 +/- 0.23 ng/mg; SHR females, 3.71 +/- 0.19 ng/mg, P < 0.01; WKY males, 1.72 +/- 0.45 ng/mg; WKY females, 2.21 +/- 0.08 ng/mg, P < 0.05, compared with SHR). Tempol reduced IsoP in SHR to levels found in WKY rats, but had no effect on IsoP in WKY rats. CONCLUSIONS: Development of hypertension in SHR is mediated in part by oxidative stress independent of sex. Also, tempol is effective in reducing blood pressure in females only when given prior to the onset of hypertension.     

Enhanced depressor response to endothelial nitric oxide synthase gene transfer into the nucleus tractus solitarii of spontaneously hypertensive rats.

Previously, we demonstrated that endothelial nitric oxide synthase (eNOS) gene transfer into the nucleus tractus solitarii (NTS) decreased blood pressure, heart rate and sympathetic nerve activity in conscious normotensive Wistar-Kyoto rats (WKY). In order to determine whether overexpression of eNOS in the NTS causes different effects on blood pressure and heart rate between spontaneously hypertensive rats (SHR) and WKY, we transfected adenovirus vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Ad beta gal) into the NTS of SHR and WKY in vivo. The local expression of eNOS in the NTS was confirmed by Western blot analysis for eNOS protein, and the magnitude of expression did not differ between SHR and WKY. Blood pressure and heart rate were monitored by the use of a radio-telemetry system in a conscious state before and 7 days after the gene transfer. Systolic blood pressure (SBP) and heart rate decreased on day 7 in both AdeNOS-transfected SHR and WKY. However, the magnitude of decreases in SBP of AdeNOS-transfected SHR was greater than that of AdeNOS-transfected WKY (-24.1 +/- 2.9 vs. -15.9 +/- 2.1 mmHg, p < 0.05). Transfection of Ad beta gal into the NTS did not alter SBP in either group. A depressor response evoked by microinjection of L-glutamate into the NTS did not differ between the two strains. These results suggest that overexpression of eNOS in the NTS causes a greater depressor response in SHR than in WKY in a conscious state. An abnormality of the L-arginine-NO pathway in the NTS may be related to the hypertensive mechanism(s) of SHR.     

A treatment with rosuvastatin induced a reduction of arterial pressure and a decrease of oxidative stress in spontaneously hypertensive rats

The aim of this study was to appreciate consequences of rosuvastatin administration on hemodynamic function, vascular oxidative stress and ischemia/reperfusion disorders in normotensive and hypertensive rats. At 10 weeks of age, spontaneously hypertensive rats (SHR, n=20) and normotensive Wistar Kyoto male rats (WKY, n=20) were divided into four groups and given, either vehicle or 10 mg/kg/day of rosuvastatin by gavage for 3 weeks. Systolic blood pressure was assessed every week. At the end of these treatments, vascular NADPH oxidase activity was evaluated by chemiluminescence (lucigenin 0.5 microM). Hearts were isolated and perfused according to the Langendorff method and were subjected to 30 min of global ischemia. Reactive oxygen species (ROS) produced during reperfusion were quantified by electron spin resonance (ESR) spectroscopy using a spin probe (CP-H, 1 mM). After one week of treatment, rosuvastatin reduced the arterial pressure in SHR rats (180.3 +/- 2.1, SHR vs 169.7 +/- 2.3 mmHg, SHR+rosuvastatin; p < 0.01), without lowering plasma cholesterol levels; these effects were not observed in WKY. NADPH activity was 25% higher in control SHR rat aortas compared to control WKY, and was reduced by rosuvastatin in SHR rats. In isolated rat hearts subjected to ischemia/reperfusion sequences, there was a deterioration in functional parameters in control SHR compared to control WKY hearts. Rosuvastatin decreased post-ischemic contracture in WKY hearts by 50% (41.5 +/- 7.5, WKY control vs 18.4 +/- 4.6 mmHg, WKY+rosuvastatin; p < 0.01) and increased left ventricular developed pressure. This beneficial effect was accompanied by a decrease in ROS detected by ESR during reperfusion (312.5 +/- 45.3, WKY control; vs 219.3 +/- 22.9 AUC/mL, WKY+rosuvastatin; p < 0.05). In conclusion, these results are in accordance with the hypothesis that oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases including hypertension, and demonstrate the beneficial effects of rosuvastatin.     

Vascular wall renin in spontaneously hypertensive rats. Potential relevance to hypertension maintenance and antihypertensive effect of captopril

Relationships among systolic blood pressure (SBP), plasma renin activity (PRA), arterial renin concentrations (ARC), and venous renin concentrations (VRC) were examined in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats before and after treatment with captopril. The ARC was elevated in SHR relative to WKY whereas VRC was not. Similarly, ARC was related to SBP (r = 0.69, p less than 0.01) whereas PRA was not (r = 0.04). Captopril (100 mg/kg daily by mouth for 8 days) decreased blood pressure significantly in both SHR and WKY. PRA as well as ARC and VRC were all increased by captopril. Bilateral nephrectomy virtually eliminated PRA but ARC was not significantly reduced over a 24-hour period. Bilateral nephrectomy also markedly attenuated the acute antihypertensive effects of captopril in SHR; however, a modest effect was still apparent. It is suggested that ARC in SHR, being higher than in WKY, may play a role in the genesis or maintenance of hypertension in this model. Furthermore, the effects of captopril in both intact and nephrectomized SHR may be related to the ability of captopril to inhibit the vascular formation of angiotensin II. Finally, vascular renin is probably not renal in origin and responds to typical feedback inhibition as unmasked by captopril administration.     

复方降压片对高血压大鼠冠状动脉壁肥厚和储备力下降的影响

目的 研究复方降压片对高血压大鼠冠状动脉壁肥厚和储备力下降的影响。方法 4w大鼠设4组：分别为自发性高血压大鼠(SHR)组、SHR口服复方降压片组、SHR口服卡托普利组和正常血压大鼠(WKY)组，饲养12w。冠脉最大血流量用离体心脏灌注法测定。结果 复方降压片能显著降低SHR收缩压、冠状动脉横截面积，提高最大冠状动脉流量，与卡托普利相似。复方降压片能降低SHR的左心室重与体重比，但仍然显著高于WKY组和口服卡托普利组。结论 复方降压片能预防SHR冠状动脉壁肥厚、储备力下降，减轻左心室肥厚；冠状动脉血流储备力的损害程度和左心室肥厚程度不平行。     

Cardiovascular responsiveness to parathyroid hormone (PTH) and PTH-related protein in genetic hypertension.

Hypertension is often accompanied by abnormalities of calcium homeostasis, including hyperparathyroidism with reduced target organ responses to PTH in kidney and bone. Due to this association between PTH and hypertension and since PTH and the paracrine factor PTH-related protein (PTHrp) have both been shown to exert marked changes in cardiovascular activity, these actions of PTH and PTHrp were examined in spontaneously hypertensive rats (SHR) and in control normotensive Wistar-Kyoto rats (WKY). Fourteen-week-old SHR [systolic blood pressure (SBP), 201 +/- 4.4 mm Hg] and WKY (SBP, 141 +/- 2.5 mm Hg) were studied. Renal cortical membranes were prepared and assayed for radioligand binding with [125I]PTH-(1-34) and [125I]PTHrp-(1-34). There was no apparent alteration in the affinity of the binding sites to either peptide in the SHR, but specific binding in SHR renal tissue was only 60% of that observed in WKY tissue for both peptides. Serum immunoreactive PTH levels were 4-fold higher in SHR than WKY, while serum total calcium and 1,25-dihydroxyvitamin D3 levels were not different. The iv administration of both PTH and PTHrp produced dose-dependent reductions in SBP and increases in heart rate in conscious unrestrained SHR and WKY. Both peptides caused greater absolute reductions in blood pressure in SHR than in WKY. However, when the hypotensive response was normalized for the higher baseline pressure in the SHR, the blood pressure reductions caused by PTH and PTHrp were not different in SHR and WKY. Conversely, the chronotropic responses to PTH and PTHrp were lower in SHR compared to WKY. These findings indicate that the SHR exhibits elevated PTH levels, with a reduced number of renal PTH/PTHrp receptors and a depressed chronotropic response to either PTH or PTHrp. In contrast, the hypotensive response to PTH or PTHrp was not altered, indicating possible tissue-specific receptor subclasses or tissue-specific regulation of PTH and PTHrp receptors.     

Prehypertensive renin-angiotensin-aldosterone system blockade in spontaneously hypertensive rats ameliorates the loss of long-term vascular function.

Arterial function after long-term hypertension is characterized by remodeling, endothelial dysfunction and reduction of previously enhanced contractile responses. We investigated whether transient prehypertensive renin-angiotensin-aldosterone system (RAAS) blockade modifies long-term arterial function. Wistar Kyoto rats (WKY) (i) and spontaneously hypertensive rats (SHR) (ii) were prehypertensively (week 4-8) treated with losartan (iii) or spironolactone (iv) (20 and 0.5 mg/kg/day, respectively) and investigated at 8 and 72 weeks of age. Systolic blood pressure (SBP) was measured intra-arterially. In isolated mesenteric arteries, active wall stress (AWS), relaxation in response to acetylcholine and wall-to-lumen ratio (W/L) were assessed. Western blotting and immunofluorescent staining of whole-mount arterial preparations and two photon laser scanning microscopy (TPLSM) were performed to quantify endothelial nitric oxide synthase (eNOS) and analyze its intracellular distribution. In 8-week-old SHR treatments were found to have reduced SBP. Relaxation, contractile responses and vascular morphology remained unaffected irrespective of treatment. At 72 weeks, SBP was similar in all SHR groups ((i) 129+/-6, (ii) 222 +/- 10, (iii) 210 +/- 16, (iv) 214 +/- 9 mmHg). Relaxation and maximum AWS were enhanced after treatments. W/L demonstrated hypertrophy ((i) 0.10 +/- 0.01, (ii) 0.16 +/- 0.02, (iii) 0.15 +/- 0.01, (iv) 0.17 +/- 0.01). Untreated SHR (p<0.01), SHR treated with losartan and SHR treated with spironolactone (p<0.05) showed less eNOS as compared to WKY. In treated SHR eNOS was concentrated in a perinuclear endothelial cell compartment. In conclusion, these findings demonstrate that transient prehypertensive blockade results in a long-lasting and blood pressure independent improvement of arterial contractility and endothelium-dependent vasodilatation that persists in aging SHR. This might be associated with an intracellular redistribution of eNOS in the endothelial cell layer.     

DOCA-salt induced malignant hypertension in spontaneously hypertensive rats

DOCA-salt hypertension was produced in 10 male 10-week-old normotensive Wistar-Kyoto (WKY) rats receiving deoxycorticosterone acetate (DOCA; 100 mg/kg, subcutaneous pellet) and 1% NaCl drinking water and was compared with data from 10 age- and sex-matched WKY receiving normal tap water (C). These data were also compared with spontaneously hypertensive (SHR) rats similarly treated. After 10 weeks on these programmes, systemic and regional haemodynamics were determined in conscious rats using microsphere techniques. DOCA-salt treatment increased mean arterial pressure (MAP), total peripheral resistance index (TPRI), cardiac and renal weights in both WKY and SHR. In contrast to SHR (C), the SHR (DOCA) demonstrated more severe MAP elevation (204 +/- 4 versus 185 +/- mmHg; P less than 0.01), more severe systemic and regional (especially renal) vasoconstriction, and malignant vasculitis associated with azotaemia and hyperuricaemia. The hyperuricaemia was related inversely to renal blood flow (r = -0.74; P less than 0.01) and directly to renal vasoconstriction (r = 0.65; P less than 0.05) in SHR (DOCA). These data suggest that in both WKY and SHR, DOCA and salt produced marked cardiovascular changes and SHR rats developed malignant hypertension.     

氯沙坦对自发性高血压大鼠左心室结构改变的实验研究

目的 :探讨氯沙坦 (Los)对自发性高血压大鼠 (SHR)左心室结构的影响。方法 :6周龄Los治疗组 (SHRlos)管饲法给予Los3 0mg kg天。治疗 17周后 ,观察 3组大鼠动脉收缩压 (SBP)、左心室 (LV)壁的厚度、左心室重量 体重 (LVW BW)以及左心室结构的变化 ;血浆放免法测肾素活性和AngⅡ含量。结果 :1 SBP :治疗结束后 ,SHRlos组血压 10 9 15± 11 3 1mmHg( 1mmHg =0 .13 3kPa) ,与对照组 (SHR)血压167 4± 13 0 1mmHg相比明显下降 (P <0 0 1)。 2 SHRlos组的LVW BW、LV壁厚度与SHR组相比明显减少 (P <0 0 1)。SHRlos心肌的超微结构与正常对照组 (WKY)相似。 3 血浆肾素活性在WKY组和SHR组之间无明显差异 (P >0 0 5 )。SHRlos组肾素活性及AngⅡ水平分别高于SHR组 (P <0 0 5 ,P <0 0 1)。结论 :Los能有效地降低SHR的血压 ,具有预防高血压LVH的作用。     

氯沙坦对自发性高血压大鼠阻力血管结构的影响

目的探讨氯沙坦（Losartan）对自发性高血压大鼠（SHR）阻力血管结构的影响,并观察在高血压血管壁增厚的过程中血管紧张素Ⅱ(AngⅡ)所起的作用。 方法采用6周龄雄性SHR20只,随机分为Losartan治疗组（SHRlos）和对照组（SHR）。另选同系雄性6周龄WKY鼠10只作为正常对照组。6周龄SHRlos给予Losartan30mg/kg/d,溶于饮水灌胃治疗17周。颈动脉插管,心电血流动力学监护仪测定动脉收缩压,应用计算机图象分析,计算血管壁腔面积比,用光镜和透射电镜观察SHR肠系膜动脉三级分支结构的变化;血浆放免法测肾素活性和AngⅡ含量。 结果（1）动脉收缩压（SBP）治疗结束后,SHR     

Genetic hypertension in the SHR rat and circulating digitalis compounds

Circulating digitalis-like compounds have been found elevated in some experimental sodium--and volume--dependent hypertensions, as well as in human essential hypertension. As few studies have been undertaken to assess their enhancement in the genetic hypertension of Okamoto (SHR) we have investigated their presence in plasma using 4 criteria: their apparent immunoreactivity with antidigoxin antibodies, their competition with tritiated ouabain binding to the sodium pump of human red blood cells,-their ability to inhibit the Na+, K+ ATPase activity of rat kidney membranes, and the Na+ fluxes from rat red blood cells. When compared to ordinary Wistar (W) and Wistar Kyoto rats (WKY), SHR exhibited a markedly enhanced apparent immunoreactivity with antidigoxin-antibodies (138 +/- 8; 59 +/- 3; 61 +/- 4 pg/ml, n = 15, 6 et 15, p less than 0.001, and p less than 0.001 respectively). The inhibition of ouabain binding by plasma extracts of the three strains did not differ (10.3 +/- 1.6, 9.9 +/- 1.7 and 12.9 +/- 1.4 ng/ml, n = 9, 18 and 14 respectively). When compared to WKY, SHR plasma extracts inhibited the renal Na+, K+ ATPase activity (75.6 +/- 2.6 vs 89.3 +/- 2.4 mumoles Pi . mg-1 . h-1, n = 11 and 10, p less than 0.01, respectively). When incubated in SHR plasma for one hour, net sodium effluxes from Wistar erythrocytes were inhibited compared to that measured in the presence of W or WKY plasma: (5.91 +/- 0.20 vs 7.68 +/- 0.25 and 7.52 +/- 0.15 mmol/l cells, n = 5, 3 and 5, p less than 0.001, and p less than 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

高血压大鼠模型主动脉僵硬度的超声多普勒评价

目的 建立一种大鼠模型超声多普勒颈-股脉搏波传播速度（PWV）准确测量方法，将其应用于自发性高血压大鼠（SHR）及其对照组中，验证该方法能否区分SHR已知增加的动脉僵硬度（AS），并探讨其应用价值。 方法 纳入雄性SHR大鼠12只，周龄、体质量相当的健康对照组Wistar Kyoto（WKY）大鼠12只。大鼠颈-股PWV的测量采用超声多普勒法完成。 结果 SHR与WKY大鼠在周龄、体长、体质量、测量期间的心率等指标对比的差异均无统计学意义。SHR大鼠的收缩压、舒张压显著高于WKY大鼠[（176 ± 4)mmHg vs (121 ± 5) mmHg，(123 ± 4) mmHg vs (85 ± 5) mmHg，均P < 0.01]；SHR大鼠的颈-股PWV测值与对照组相比显著增高[（6.5 ± 1.0)m/s vs (4.5 ± 0.9) m/s, P < 0.01]；Bland-Altman一致性检验显示两组大鼠的颈-股PWV测值在观察者间具有良好的重复性。 结论 超声多普勒颈-股PWV测量方法能够精确测量SHR大鼠模型脉搏波传播时间和距离，藉以评价其AS。基于超声多普勒的PWV测量是一种评价大鼠模型AS的可靠方法。     

Exercise training causes skeletal muscle venular growth and alters hemodynamic responses in spontaneously hypertensive rats

OBJECTIVE: To investigate whether training changes skeletal muscle venular profile and hemodynamic responses to exercise we studied spontanesouly hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats submitted to training programme (T = 50-60% of VO2max). DESIGN: Training (T) was performed on a treadmill over a period of 13 weeks. Age-matched control groups were kept sedentary (S). T and S rats were chronically instrumented for hindlimb flow (HLF) and arterial pressure (AP) measurements at rest, during dynamic exercise and recovery in two different situations: control and after extensive intravenous blockade (hexamethonium + losartan + Nomega-nitro-L-arginine methyl ester + hydralazine). For morphometric analysis, skeletal muscle samples (gracilis) were obtained after transcardiac perfusion with fixative. RESULTS: T caused a significant reduction of resting mean arterial pressure (MAP) (-11%) only in the SHR group without changing basal HLF. In the sedentary SHR (SHRs), basal relative hindlimb resistance was increased by 45%, but was significantly reduced after T (P < 0.05). During dynamic exercise, MAP increased similarly (10-20 mmHg) in all groups. HLF increases were similar for the four groups up to 0.8 km/h; at higher workloads, HLF was higher in trained SHR (SHRT) versus trained WKY (WKYT) (3.9- versus 2.9-fold increase over basal HLF, respectively). After blockade (and pressure correction with IV phenylephrine infusion), steady-state exercise was performed with similar hindlimb vasodilation in all groups and was accompanied by MAP reduction (-17 +/- 8 mmHg) only in SHRT group. Skeletal muscle venular profile (density, diameter and lumen cross-sectional area) was similar in WKY(T), WKY(S) and SHR(S), but significantly increased in SHR(T). In this group the two-fold increase in venule density was correlated with both the reduction in baseline MAP and the increase in HLF during dynamic exercise. CONCLUSIONS: The results suggest that increased venule density is a specific adaptation of SHR skeletal muscle to training. Venular growth may contribute to both the pressure-lowering effect and the large HLF at high exercise intensities observed in the trained SHR.