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1.
To investigate the role of nerve growth factor (NGF) in the development of hypertensive renal vascular remodeling, antiserum against NGF (anti‐NGF) or vehicle was injected at 3 weeks of age in spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rats (n = 9 for each treatment in each strain). Flow‐pressure (F‐P) and pressure‐glomerular filtration rate (P‐GFR) relationships at vasodilated perfused kidneys were determined at 10 weeks of age. In the vehicle rats, blood pressure, renal noradrenaline content, the gradient of F‐P (minimal vascular resistance at pre‐ and post‐glomerular vasculature) and the X‐intercept of P‐GFR (preglomerular : postglomerular vascular resistance ratio) were greater in SHR than in WKY rats, although the gradient of P‐GFR (glomerular filtration capacity) did not differ significantly between the strains. Blood pressure and renal noradrenaline content were lower in SHR receiving anti‐NGF than in SHR receiving vehicle, although such difference was not observed in WKY rats. The gradient of F‐P was less but the gradient of P‐GFR was greater in SHR receiving anti‐NGF compared with SHR receiving vehicle, although the similar differences did not occur in WKY rats. Blood pressure and renal noradrenaline content remained greater in SHR treated with anti‐NGF compared with WKY rats treated with vehicle; however, the gradient of F‐P did not differ significantly between them. Contrary, anti‐NGF did not affect the X‐intercept of P‐GFR in either strain. In conclusion, NGF could contribute to the genesis of renal vascular remodeling, at least in part, through modification of renal sympathetic activity and blood pressure in SHR.  相似文献   

2.
罗沙坦对自发性高血压肾小动脉重建的逆转作用   总被引:1,自引:0,他引:1  
目的 研究血管紧张素Ⅱ受体拮抗剂罗沙坦对高血压肾小动脉重建的逆转作用。方法  16wk龄 大鼠分为 :正常血压大鼠 (WKY)组、自发性高血压大鼠 (SHR)对照组、罗沙坦治疗高剂量组 (15mg·kg-1·d-1)和罗沙坦治疗低剂量组 (0 75mg·kg-1·d-1)。每组 6只大鼠 ,饲养 10wk。在肾组织切片上用光镜结合计算机图像分析法观测肾内小动脉的几何形态学指标 ,离体肾脏灌流法测定最小肾血管阻力。结果 罗沙坦高剂量组的尾动脉收缩压、肾内小动脉壁厚、壁面积、壁厚内径比和最小肾血管阻力 ,均较高血压对照组显著下降或减小 ;罗沙坦低剂量组的肾内小动脉壁厚和壁厚内径比较高血压对照组显著下降或减小。结论 AngⅡ受体拮抗剂能逆转SHR肾小动脉的重建 ,而且是非血压依赖性的  相似文献   

3.
4.
1. The level of hypertension displayed by the adult spontaneously hypertensive rat (SHR) may be reduced by 20-30 mmHg if SHR pups are cross-fostered to a normotensive dam at birth (SHRX). The mechanisms involved are largely unknown, but may involve the kidney and the renin-angiotensin system (RAS) because renal responses to angiotensin (Ang) II are enhanced in the SHR and brief blockade of the RAS in the young rat permanently lowers blood pressure in the SHR. Accordingly, the aim of the present study was to investigate the effect of cross-fostering on the renal response to AngII in the SHR. 2. Renal function was studied in anaesthetized 4-week-old SHR, cross-fostered SHRX and control Wistar-Kyoto (WKY) rats. Standard clearance methods were used to investigate the renal haemodynamic and tubular effects of AngII. The nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was coinfused in some experiments to abolish the counterbalancing effect of nitric oxide. 3. Angiotensin II induced a fall in glomerular filtration rate (GFR) in both SHR and SHRX, but not in WKY rats. This was accompanied by a significant reduction in sodium excretion by SHR but not SHRX pups. This effect appeared to be tubular in origin, because sodium clearance was comparable between the two strains after AngII, but fractional sodium excretion was significantly higher in the SHRX. Coinfusion of the NOS inhibitor L-NAME had little further effect on sodium excretion in SHR and SHRX, but restored GFR in SHRX to levels comparable with those in WKY rats. 4. These data suggest that renal tubular sensitivity to AngII in the SHR can be altered during the early stages of postnatal development, which may contribute to the blood pressure- lowering effect of cross-fostering in the SHR.  相似文献   

5.
Total body sodium of male and female spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats was estimated weekly during the first 8 weeks of life by measuring exchangeable sodium (ENa). Blood pressure and sodium intake was measured from weeks 4 to 8. SHR had significantly higher blood pressure and sodium intake than WKY from 4 to 8 weeks of age. ENa was higher in SHR than WKY throughout the first 8 weeks of life. Relative sodium retention was observed in SHR during weeks 5 to 8 despite a significant rise in SHR blood pressure and fall in sodium intake. These findings suggest a change in the renal pressure/natriuresis relationship at this age in the SHR.  相似文献   

6.
1. The hypotensive effect of cross-fostering in spontaneously hypertensive rats (SHR) is thought to involve adjustments in renal function. However, its association with renal anti-oxidant/oxidant balance during cross-fostering is not known. 2. The present study examined the effect of cross-fostering and in-fostering of 1-day-old offspring between SHR and Wistar-Kyoto (WKY) dams on renal anti-oxidant/oxidant status and systolic blood pressure (SBP). Renal anti-oxidant/oxidant status and SBP were determined in the offspring from 4-16 weeks of age. 3. Cross-fostered SHR had significantly lower SBP than in-fostered SHR at 6, 8 and 12 weeks, but not at 16 weeks (127 ± 1 vs 144 ± 2, 138 ± 1 vs 160 ± 1, 174 ± 2 vs 184 ± 2 and 199 ± 2 vs 194 ± 3 mmHg at 6, 8, 12 and 16 weeks, respectively). No differences in SBP were evident between cross-fostered and in-fostered WKY rats. There were no significant differences in levels of thiobarbituric acid-reactive substances (TBARS), protein carbonyl and total anti-oxidant status (TAS) or superoxide dismutase, catalase, glutathione peroxidase (GPx), glutathione S-transferase and glutathione reductase activity between cross-fostered and in-fostered SHR or WKY offspring. However, compared with WKY rats, catalase activity was higher at 6 and 16 weeks, TAS was higher at 16 weeks and GPx activity and TBARS were lower at 16 weeks in SHR. 4. It appears that cross-fostering of SHR offspring to WKY dams during the early postnatal period causes a transient delay in the rise in blood pressure in SHR and that this does not involve the renal anti-oxidant/oxidant system.  相似文献   

7.
This study examines the effects of a 6-week exposure to 1% NaCl in tap water with and without desoxycorticosterone acetate (DOCA) on renal alpha adrenoceptors and systolic blood pressure (SBP) in spontaneously hypertensive adult rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. On normal sodium intake, SHR had higher renal alpha 1- (p less than 0.05) and alpha 2-adrenoceptor densities (p less than 0.001) and SBP (p less than 0.001) than WKY rats. Although WKY rats given either 1% NaCl, DOCA, or DOCA plus 1% NaCl developed hypertension after 6 weeks of treatment, only 1% NaCl administration for the same period produced an increase in the alpha 1-adrenoceptor density when compared to the control (p less than 0.001). In SHR, ingestion of 1% NaCl or DOCA plus 1% NaCl increased the already elevated alpha 2-adrenoceptor density (p less than 0.001) and SBP even more in this strain after 6 weeks of treatment. Equilibrium dissociation constants (Kd), however, were similar for both classes of receptors in experimental and control rats. The results of this study indicate that only the combination of 1% NaCl in tap water and DOCA administration is effective in accelerating hypertension in adult SHR. On the other hand, in this form of genetic rat hypertension, exaggerated sodium intake with or without DOCA administration could presumably be correlated with the increased renal alpha 2 adrenoceptors observed in these animals.  相似文献   

8.
1. Several lines of evidence indicate that thromboxane (Tx) A2 may contribute to the development and maintenance of hypertension. The present study was undertaken to evaluate the role of TxA2 in the development of hypertension in spontaneously hypertensive rats (SHR) by using an orally active, highly specific TxA2/prostaglandin H2 receptor antagonist S-1452. 2. Vehicle (1% arabic gum solution) alone was given orally to Wistar-Kyoto (WKY) rats (n = 15) and SHR (n = 14), while S-1452 (10 mg/kg per day, twice daily) was administered orally to SHR (n = 16) for 18 weeks (from 5 to 23 weeks of age). 3. No significant difference was observed in tail-cuff blood pressure (BP) between vehicle- and S-1452-treated SHR before and at 5 and 11 weeks after treatment. Thereafter, BP was further elevated in vehicle-treated SHR, but was significantly blunted in SHR treated with S-1452 at 15 (224+/-8 vs 211+/-13 mmHg; P < 0.01) and 18 weeks (227+/-9 vs 206+/-10 mmHg; P < 0.001); this was associated with reduced proteinuria. 4. Urinary TxB2 in vehicle-treated SHR, especially during the early period, was significantly greater than that in WKY rats, while no significant difference was observed in urinary 6-ketoprostaglandin F1alpha (6-keto-PGF1alpha) between the two groups. Treatment with S-1452 reduced urinary excretion of TxB2 at 18 weeks. 5. The present study shows that S-1452, at the dose used, does not reduce BP during the early period of the development of hypertension. These results suggest that the role of enhanced TxA2 production in the development of hypertension is small, if any, in SHR. Delayed response of BP may be independent of the direct pharmacological effects of S-1452.  相似文献   

9.
We evaluated the role of chronic cardioselective beta-adrenoceptor blockade in left ventricular (LV) function in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Commencing at 4 weeks of age, the animals were injected twice daily (20 mg/kg) with atenolol and were studied at either 10 or 16 weeks of age, to compare the stages of developing and established hypertension in SHR. Both blood pressure and LV mass were attenuated in the treated SHR. Ventricular function-evaluated by increasing preload (infusion of Tyrode solution) and recording indices of peak cardiac output, i.e., cardiac index (CI), stroke index (SI), and acceleration of flow-was similar in SHR and WKY at both 10 and 16 weeks of age. At 10 weeks, peak CI and SI were not significantly different in treated and non-treated SHR. By 16 weeks, however, atenolol treatment was associated with a significant decrease in peak CI (20%) attributable mainly to a lower SI. LV end-diastolic and systolic pressures were not affected by chronic treatment with the beta-adrenoceptor antagonist. It is concluded that, when prolonged atenolol treatment is initiated during early postnatal life, peak LV function in SHR is compromised.  相似文献   

10.
1. To investigate effects of a reduction in nephron numbers on renal structural properties in hypertension, either unilateral nephrectomy (UNX) or sham operation (SO) was performed at 5 weeks of age in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 9 for each operation for each strain). 2. At 10-12 weeks of age, flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships were determined for maximally vasodilated, perfused kidneys. Kidneys were then perfusion fixed for histological analysis. 3. In the SO groups, the slope of F-P (minimal renal vascular resistance, reflecting overall luminal dimensions of pre- and post-glomerular vasculature) was greater in SHR than in WKY rats. The threshold pressure for beginning filtration at P-GFR (preglomerular to post-glomerular vascular resistance ratio) was higher in SHR than in WKY rats, but the slope of P-GFR (glomerular filtration capacity) did not differ between the two strains. These results suggest that vascular narrowing occurred, especially in the preglomerular resistance vessels in the kidneys of SHR, although glomerular filtration capacity was normal. 4. In UNX animals, the following results were obtained: (i) the slope of F-P was not affected in either strain; (ii) the pressure for beginning filtration at P-GFR was unchanged in WKY rats, but was decreased in SHR; (iii) the slope of P-GFR increased in WKY rats, but a compensatory adaptive increase was missing in SHR; and (iv) histologically, small increases in the luminal cross-sectional area of interlobular arteries and glomerular tuft area were observed in both strains. However, the increase in vascular lumen was more pronounced in SHR, whereas glomerular enlargement was greater in WKY rats. 5. These results suggested that UNX attenuates vascular narrowing of the preglomerular resistance vessels and glomerular structural adaptations to UNX (i.e. increased filtering capacity and glomerular enlargement) are impaired in SHR.  相似文献   

11.
1. The effects of an oral daily dose (10 mg kg(-1)) of the flavonoid quercetin for 5 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. 2. Quercetin induced a significant reduction in systolic (-18%), diastolic (-23%) and mean (-21%) arterial blood pressure and heart rate (-12%) in SHR but not in WKY rats. 3. The left ventricular weight index and the kidney weight index in vehicle-treated SHR were significantly greater than in control WKY and these parameters were significantly reduced in quercetin-treated SHR in parallel with the reduction in systolic blood pressure. 4. Quercetin had no effect on the vasodilator responses to sodium nitroprusside or to the vasoconstrictor responses to noradrenaline or KCl but enhanced the endothelium-dependent relaxation to acetylcholine (E(max)=58+/-5% vs 78+/-5%, P<0.01) in isolated aortae. 5. The 24 h urinary isoprostane F(2 alpha) excretion and the plasma malonyldialdehyde (MDA) levels in SHR rats were increased as compared to WKY rats. However, in quercetin-treated SHR rats both parameters were similar to those of vehicle-treated WKY. 6. These data demonstrate that quercetin reduces the elevated blood pressure, the cardiac and renal hypertrophy and the functional vascular changes in SHR rats without effect on WKY. These effects were associated with a reduced oxidant status due to the antioxidant properties of the drug.  相似文献   

12.
Dynorphin receptor binding sites in hippocampal membrane preparations were assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 4, 8, 12 and 16 weeks of age. At 4 weeks of age, before hypertension is manifested, SHRs had significantly more hippocampal dynorphin receptor binding sites than WKY controls. At 8, 12 and 16 weeks of age, however, when hypertension is seen, SHRs showed significantly fewer hippocampal binding sites than WKY rats. No receptor affinity changes for dynorphin were seen between the two strains of rats at any age. These results suggest that hippocampal receptor changes involving the opioid system may play a role in the central component of blood pressure control.  相似文献   

13.
In spontaneously hypertensive rats (SHRs) the dopaminergic D1-like renal vasodilator response is impaired. The renal vascular response to D2-like receptor stimulation in vivo is incompletely known. Therefore, renal hemodynamics were studied in conscious SHRs during continuous infusion of D2-like agonist N,N-Di-n-propyldopamine (DPDA) (10 microg/kg/min) with Wistar-Kyoto (WKY) rats as controls. As sodium status may affect dopaminergic responses, rats were studied during both low- and high-sodium diets. D2-like stimulation reduced mean arterial pressure and effective renal plasma flow and glomerular filtration rate (GFR) similarly in SHR and WKY rats. Renal vascular resistance increased significantly in both strains. The response to DPDA is modified by sodium status, with a more pronounced fall in blood pressure (in WKYs and SHRs) and GFR (in WKYs) during high-sodium conditions. The responses were blocked by co-infusion with D2 antagonist domperidone. Thus, D2-like renal vascular responses are normal in SHRs irrespective of sodium intake. The combination of a preserved D2-like renal vasoconstrictive and an impaired D1-like renal vasodilatory response may contribute to maintenance of hypertension in SHRs.  相似文献   

14.
Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, has been proposed to play a pathophysiologic role in hypertension. The aim of this study was to find out whether changes in ET-receptor function are cause or consequence of blood pressure elevation in hypertension. For this purpose, we assessed ET-receptor function [as ET-1-induced [3H]inositol phosphate (IP) accumulation] in slices of left ventricle and renal cortex and in rings of thoracic and abdominal aorta from spontaneously hypertensive rats (SHR) at the age of 8 weeks (i.e. developing hypertension), 12 and 24 weeks (established hypertension) vs. normotensive age-matched Wistar-Kyoto (WKY) rats, and from supra-renal aortic-banded (AOB) rats at the age of 8, 12 and 24 weeks (i.e. 4, 8 and 20 weeks after AOB) vs. sham-operated (SOP) age-matched WKY rats. In the SHR with established hypertension ET-1-induced IP formation was altered in all tissues investigated: it was significantly increased vs. WKY rats in left ventricle, and significantly decreased in renal and aortic tissues. Similarly, in AOB rats at all ages ET-1-induced IP formation was changed in those tissues that were under pressure load [heart (increase) and thoracic aorta (decrease)] vs. SOP rats, whereas in those tissues not under pressure load (kidney and abdominal aorta) ET-1-induced IP formation was not different between AOB and SOP rats. Moreover, in 8-week-old SHR (where hypertension is not yet established) ET-1-induced IP formation was not significantly different compared to WKY rats (with the exception of thoracic aorta). We conclude that, at least in SHR and AOB rats, changes in ET-1 signalling are secondary to the elevation in blood pressure.  相似文献   

15.
Renal norepinephrine (NE) content was determined during the development of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats in an attempt to correlate biochemical changes with the reported functional changes occurring in hypertension development in the SHR. In contrast to WKY rats, in which the levels of NE remained relatively constant with age, renal NE content in the SHR was highest at the 4th week of age, decreasing transiently during the 5th, 6th, and 7th weeks, and then again reaching a plateau during the 8th week. The fall in NE content in the kidney is associated with a rise in blood pressure with age in SHR and suggests a relationship between NE levels and hypertension.  相似文献   

16.
1. Inhibition of the renin-angiotensin system (RAS) during kidney development produces chronic alterations in renal morphology and function that have been characterized in detail in adult animals. The aim of the present study was to determine the consequences of neonatal angiotensin-converting enzyme (ACE) inhibition on renal haemodynamics and function in rats at a much earlier age, namely 3-4 weeks. 2. Male Wistar pups received daily intraperitoneal injections of enalapril (10 mg/kg) or isotonic saline from birth until 24-28 days of age, when renal haemodynamics and function were assessed using clearance techniques under pentobarbital anaesthesia. 3. Enalapril-treated rats showed significant reductions in glomerular filtration rate (GFR; -44 +/- 6%; P < 0.05), effective renal plasma flow (ERPF; -33 +/- 6%; P < 0.05) and filtration fraction (-16 +/- 3%; P < 0.05) compared with saline-treated controls. Although mean arterial pressure tended to be lower in enalapril-treated rats, this group demonstrated a significant increase in renal vascular resistance compared with control rats (RVR; 46 +/- 6 vs 32 +/- 3 mmHg/mL per.min per g.kidney weight, respectively; P < 0.05). In enalapril-treated rats, urine osmolality was reduced (-59 +/- 5%; P < 0.05) and urine flow rate and fractional urinary excretion rates of sodium and potassium were markedly elevated compared with controls (P < 0.05). Enalapril-treated rats showed severe renal histological abnormalities, including wall thickening of cortical arterioles, papillary atrophy and tubulointerstitial alterations, mimicking those described previously in similarly treated rats examined in adulthood. 4. In conclusion, neonatal ACE inhibition in rats induces pronounced alterations in renal haemodynamics and function, characterized by reductions in ERPF and GFR, increased RVR and impaired tubular sodium and water reabsorption, which are evident at weaning.  相似文献   

17.
Up-regulation of kidney α2-adrenoceptor expression has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). This study was carried out to evaluate renal sodium excretion in response to clonidine administration in SHR and control normotensive Wistar-Kyoto (WKY) rats. SHR and WKY rats (12-week-old) were placed in metabolic cages for 4 days: the first 2 days in control conditions and the following 2 days under oral clonidine treatment (100 μg/kg body weight). Clonidine produced a similar reduction in systolic blood pressure values in SHR and WKY rats, although SHR remained hypertensive. At the end of the study SHR and WKY rats presented similar noradrenaline plasma levels. However, noradrenaline kidney tissue levels were significantly higher in SHR compared to WKY rats. Under control conditions, SHR presented lower urine flow compared to WKY rats. Clonidine produced a significant decrease in urine flow in WKY rats but not in SHR. Furthermore, clonidine also produced a significant reduction in urinary sodium, potassium, and creatinine excretion in WKY rats, but had no effect in SHR. In conclusion, in SHR the reduction in systolic blood pressure and sympathetic activity produced by clonidine was not accompanied by a decrease in urine volume and sodium excretion.  相似文献   

18.
When CV-4151, a specific thromboxane (TX) A2 synthetase inhibitor, was given orally to 4 week old (4w) spontaneously hypertensive rats (SHR) daily for 3 weeks, the initiation of hypertension was delayed by about one week. The agent increased urinary excretion of water, sodium and creatinine, reduced that of TXA2 (as TXB2), increased that of PGI2 (as 6-keto-PGF1 alpha) and enhanced urinary PGI2/TXA2. In 4w Wistar-Kyoto rats (WKY) and 18w SHR was established hypertension, the agent had little effect on blood pressure and renal function. In isolated, perfused kidneys of 6w SHR, CV-4151 markedly inhibited both arachidonic acid-induced pressor action and production of TXA2. TXA2 synthetase activity in renal cortical microsomes of 5w SHR was approximately 1.5 times higher than that in age-matched WKY. CV-4151 inhibited TXA2 synthetase activity of medullary and cortical microsomes more effectively in 5w SHR than in age-matched WKY. Thus, in young SHR, the TXA2 synthetase inhibitor seemed to improve renal function by altering the balance of renal TXA2 and PGI2 biosynthesis and subsequently caused a delay in the initiation of hypertension. The present findings lend support to the idea that an imbalance in the renal TXA2-PGI2 biosynthesis may be involved in the initiation of hypertension in SHR.  相似文献   

19.
The effects of successive injections of the alpha-adrenoceptor agonist clonidine (25, 50 and 100 ug/kg given at hourly intervals) on the body temperature of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, previously treated for 48 hr with slow release emulsions (subcutaneous) containing either morphine (morphine SR, 100 mg/kg), naloxone (naloxone SR, 80 mg/kg) or no drug (vehicle SR), were examined. The successive injections of clonidine produced dose-dependent falls in body temperature which were quantitatively similar in the vehicle-treated WKY and spontaneously hypertensive rats. The hypothermic effects of clonidine in the morphine-dependent WKY and spontaneously hypertensive rats, and in the naloxone-treated WKY and spontaneously hypertensive rats, were not different to those of the respective vehicle-treated controls. These results suggest that endogenous mu-receptor opioid peptides do not have a major involvement in the hypothermic actions of clonidine, in either normotensive or spontaneously hypertensive rats.  相似文献   

20.
1. To investigate whether the difference in the SA gene expression in the kidneys is causally related to the pathogenesis of hypertension, we reassessed the expression of the SA gene in the kidneys of the spontaneously hypertensive rat (SHR), its stroke-prone substrain (SHRSP) and Wistar-Kyoto (WKY) rat from different sources (SHR/Izm, SHRSP/Izm and WKY/ Izm from Izumo colony; SHR/Crj and WKY/Crj from Charles River Laboratories). 2. At the age of 5 weeks, high levels of the SA mRNA were expressed in the kidneys of SHRSP/Izm, SHR/Izm, SHR/Crj and WKY/Izm, while very low levels of the SA mRNA were observed in those of WKY/Crj. At the age of 8 weeks, the expression of the SA mRNA in the kidneys of WKY/Izm was at the same level as in those of SHRSP/Izm and two SHR strains. 3. Four genetic markers at the SA locus, an StuI restriction fragment length polymorphism and three microsatellite markers, were not polymorphic among Izumo strains of SHR, SHRSP and WKY rats. 4. In situ hybridization showed strong signals of the SA mRNA in the renal proximal tubules, while no positive signals were detected in the glomeruli. 5. Because WKY/Izm has normal blood pressure, our observations indicate that a simple difference of the SA gene expression in the kidney cannot be an explanation for the difference of blood pressure between SHR(SP)/Izm and WKY/Izm.  相似文献   

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