HYPOTENSIVE EFFECT OF CHRONICALLY INFUSED ADRENOMEDULLIN IN CONSCIOUS WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS

1. The hypotensive effect of chronically infused human adrenomedullin (hAM), a potent vasodilator peptide that has been reported to have a natriuretic action, was examined in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Conscious WKY rats and SHR were infused with 200 ng/h synthetic hAM for 14 days by means of osmotic minipumps. Control groups were infused at the same schedule with 0.9% saline. Systolic blood pressure (SBP) and daily urinary excretion of Na⁺ and K⁺ were measured before and during the infusion period. In addition, plasma renin activity (PRA), aldosterone and hAM concentrations were measured on day 14 of infusion. 3. A significant reduction in SBP was observed in hAM-treated SHR at day 2 and SBP remained significantly lower throughout the experiment compared with control SHR. Similarly, SBP in the hAM-treated WKY rats was found to be significantly lower than in control WKY rats during infusion. However, the hypotensive effect was not accompanied by any significant increase in urinary volume or Na⁺ excretion in hAM-treated rats of either strain. Chronic infusion with hAM significantly suppressed PRA and lowered the concentration of plasma aldosterone in WKY rats but not in SHR. The plasma hAM levels in treated WKY rats and SHR were 0.0 ± 9.4 and 0.6 ± 0.2 fmol/mL, respectively. 4. These findings demonstrate that chronically infused hAM has a hypotensive effect in both WKY rats and SHR without an increase in urinary volume or Na⁺ excretion at a plasma AM concentration within the physiological limit.     

Captopril avoids hypertension,the increase in plasma angiotensin II but increases angiotensin 1–7 and angiotensin II‐induced perfusion pressure in isolated kidney in SHR

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Effects of an angiotensin-converting enzyme (ACE) inhibitor, SA446, on tissue ACE activity in normotensive, spontaneously hypertensive, and renal hypertensive rats

Effects of an angiotensin-converting enzyme (ACE) inhibitor, SA446, on the renin-angiotensin system, particularly on tissue ACE activity, were studied in Wistar-Kyoto normotensive rats (WKY), spontaneously hypertensive rats (SHR), and two-kidney, one-clip renal hypertensive rats (RHR) by repeated oral administration for 7 days. SA446 (45 mg/kg/day p.o.) inhibited ACE activity in the lung, brain, kidney, heart, and whole blood throughout the administration period in WKY, but showed a slight hypotensive action and no inhibition of aorta ACE activity. On the other hand, SA446 had an apparent hypotensive action at the same dose in SHR and inhibited ACE activity significantly in the aorta as well as the kidney and whole blood during the administration period. Furthermore, enzyme activity in the aorta, kidney, heart, and whole blood was also inhibited at a hypotensive dose of SA446 (10 mg/kg/day p.o.) in RHR. The inhibition in whole blood and kidney was almost complete, and the inhibition in the aorta was greater on day 7 than on day 1. The maximum decrease of blood pressure was correlated with the maximum inhibition in aorta ACE activity, but not in brain, lung, or heart ACE activity. In addition, a good positive correlation was observed between the basal blood pressure and the basal aorta ACE activity in WKY, SHR, and RHR, although there was no correlation in the brain, lung, kidney, heart, or whole blood. These results suggest that the antihypertensive action of SA446 by repeated administration may be due to inhibition of arterial ACE activity in addition to inhibition of plasma and kidney ACE activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

RE-EVALUATION OF THE SA GENE IN SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

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.     

PATHOGENETIC ROLE OF VASCULAR ANGIOTENSIN-CONVERTING ENZYME IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. This study was undertaken to examine the possibility that the level of angiotensin-converting enzyme (ACE) increases in vascular tissue, and that this may participate in the pathogenesis of hypertension in spontaneously hypertensive rat (SHR). 2. In SHR, at the established hypertensive stage, the prolonged antihypertensive effect induced by a single oral dose of spirapril was closely correlated to the long-lasting inhibition of ACE in aortae and mesenteric arteries. In contrast, ACE in plasma, lung, heart and kidney recovered from inhibition faster than in vessels. 3. Prolonged daily oral treatment of SHR with spirapril, initiated at the age of 8 weeks and continued for 8 weeks, prevented the development of hypertension with concomitant decrease in aortic ACE activity. Blood pressure continued to be suppressed after the drug was withdrawn, as did the aortic ACE activity. 4. Spontaneously hypertensive rats developed hypertension with age as well as with the increase in aortic ACE activity which became higher with age than that of Wistar-Kyoto (WKY) normotensive control rats. On the contrary, ACE activity in plasma and lung of SHR was substantially lower than that of WKY at any age from 4 to 20 weeks old. Brain ACE activity of SHR did not differ from that of WKY at any age. Aged SHR showed the lower enzyme activity in the kidney compared with that of age-matched WKY. 5. Our results support the hypothesis that increased vascular ACE may play an essential role in the development and maintenance of hypertension in SHR.     

Effect of polyphenol-containing azuki bean (Vigna angularis) extract on blood pressure elevation and macrophage infiltration in the heart and kidney of spontaneously hypertensive rats

1. Hypertension is a major risk factor for myocardial infarction and renal damage, and it has also been shown to have pro-inflammatory actions that increase the formation of reactive oxygen species. Macrophage infiltration has been suggested to play a role in the pathogenesis of hypertension. Azuki beans are known to contain pro-anthocyanidins, a group of polyphenolic bioflavonoids with remarkable radical-scavenging activities in vitro. Therefore, the aim of the present study was to investigate the effect of polyphenol-containing azuki bean extract (ABE) on systolic blood pressure (SBP) and macrophage infiltration in the heart and kidney of spontaneously hypertensive rats (SHR). 2. Spontaneously hypertensive rats and control normotensive Wistar-Kyoto (WKY) rats were divided into two groups fed either 0 or 0.8% ABE in their diets. Tail SBP and macrophage kinetics in the heart and kidney were examined. 3. The SBP of the SHR group was higher than that of age-matched WKY rats throughout the treatment period. After 8 weeks of treatment, the increased SBP in ABE-treated SHR was significantly less than that in untreated SHR. 4. Nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH)-stimulated superoxide (O2-) production was enhanced in the kidney and heart in SHR and WKY rats compared with levels in the absence of NADH or NADPH. The NADPH-stimulated superoxide (O2-) levels in the kidney in untreated SHR was significantly higher than that in untreated WKY rats. The (O2-) levels in ABE-treated SHR were significantly decreased compared with the untreated SHR group. 5. In immunohistochemical analyses, the number of macrophages in the heart and in the glomeruli and tubulointerstitium of the kidney was significantly higher in ABE-untreated SHR than in ABE-untreated WKY rats. Conversely, there was a significant decrease in the number of macrophages in ABE-treated SHR compared with the untreated SHR. There were significant positive correlations between SBP and the number of ED1-positive macrophages in the heart and tubulointerstitial and glomerular areas of the kidney in WKY rats and SHR. 6. In conclusion, the results of the present study suggest that ABE attenuates the elevation of SBP and macrophage infiltration in the heart, as well as in the glomeruli and tubulointerstitium of the kidney, in our SHR model.     

Effect of captopril on converting enzyme activity in chemically sympathectomized, spontaneously hypertensive rats

Effect of subacute angiotensin converting enzyme (ACE) blockade on the converting enzyme activity (ACE activity) in plasma, aorta, lung, kidney and whole brain was evaluated in chemically-sympathectomized (with 6-hydroxydopamine) normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) using captopril given peripherally via the intraperitoneal (i.p) route and centrally through intracerebroventricular (i.c.v.) administration. Daily i.p. injection of 25 mg/kg for 8 days reduced the blood pressure of both WKY rats and SHR, and the ACE activity in the aorta, lung and plasma of both WKY rats and SHR were correspondingly depressed. The brain ACE activity remained unaltered in both strain of rats. The ACE activity in the kidney of WKY was depressed, while that of SHR remained unchanged. These observations are independent of peripheral sympathectomy with 6-hydroxydopamine (6-OHDA). Daily central captopril administration at a dose of 2 mg/kg, i.c.v., for 8 days significantly reduced the blood pressure of SHR but not WKY rats, whereas the ACE activity of the whole brain of both WKY and SHR were depressed. Central sympathectomy with 6-OHDA did not alter these responses. It is concluded that captopril exerts its antihypertensive effect not only via reduction of the ACE activity in the plasma and lungs as reported earlier, but also that of other organs, principally the aorta, and that these effects are independent of the sympathetic nervous system.     

TRANSPLANTATION STUDIES OF THE ROLE OF THE KIDNEY IN LONG-TERM BLOOD PRESSURE REDUCTION FOLLOWING BRIEF ACE INHIBITOR TREATMENT IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

1. Brief treatment with angiotensin-converting enzyme (ACE) inhibitors in young spontaneously hypertensive rats (SHR) causes a persistent reduction in blood pressure associated with a relatively selective reduction in renal vascular resistance. 2. To study the possible role of the kidney in this long-term hypotensive effect, we transplanted kidneys from untreated SHR into SHR that had been treated with perindopril (3 mg/kg per day) between 6 and 10 weeks of age and also transplanted kidneys from perindopril-pretreated SHR into untreated SHR. After transplantation, the remaining native kidney was removed so that only donor kidneys remained. 3. Untreated SHR that received kidneys from perindopril-pretreated SHR showed an initial fall in blood pressure followed by a rapid increase in pressure, weight loss and early death. 4. The transplantation of kidneys from control SHR into perindopril-pretreated SHR resulted in a rise in blood pressure that obviated the long-term reduction seen normally in these animals. 5. Kidneys from perindopril-pretreated SHR may be susceptible to the high blood pressure in untreated SHR. 6. The blood pressure increase in perindopril-pretreated SHR that accompanies substitution of the native kidneys by kidneys from untreated SHR further supports the hypothesis that the kidney is responsible for the long-term pressure effects following ACE inhibition in young SHR.     

阿托伐他汀对自发性高血压大鼠血压和细胞色素P450表氧化酶2C11基因表达的影响

目的研究阿托伐他汀降低自发性高血压大鼠(SHR)血压的作用是否与其调节细胞色素P450表氧化酶2C11(CYP2C11)基因表达的作用有关。方法18只SHR随机分为SHR模型组、阿托伐他汀50和10 mg.kg-1组;6只W istar-Kyoto大鼠(WKY)作为正常对照组。阿托伐他汀ig给药,每日1次,共10周。分别于给药前和给药后每2周测量大鼠尾动脉收缩压(SBP);RT-PCR和W estern印迹法分别检测心、肝、肾及主动脉组织中CYP2C11mRNA和蛋白质表达;ELISA方法检测尿液中14,15二-氢二十碳三烯酸(DHET)含量;并测定血脂含量。结果阿托伐他汀50 mg.kg-1组在给药后第6~10周和10 mg.kg-1组在给药后第10周SBP明显低于SHR模型组。在CYP2C11 mRNA和蛋白质表达中,SHR模型组心、肾和主动脉均明显高于WKY组;给药10周后,阿托伐他汀50 m.gkg-1组的4种组织和10 m.gkg-1组的心、肾和主动脉的表达明显高于SHR模型组。治疗前SHR各组尿液中DHET的含量均显著高于WKY组,给药后阿托伐他汀50 m.gkg-1组的含量明显高于SHR模型组;同时,阿托伐他汀50 mg.kg-1组血脂水平明显低于SHR模型组。结论阿托伐他汀可上调CYP2C11基因的表达,并增加其代谢产物表氧化二十碳三烯酸,这可能是其降低血压的作用机制之一。     

Effects of exercise training on nitric oxide synthase in the kidney of spontaneously hypertensive rats

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PRODUCTION OF EICOSANOIDS AND ANGIOTENSIN II IN RESISTANCE VESSELS IN SPONTANEOUSLY HYPERTENSIVE RATS

1. Angiotensin II (Angll) and eicosanoids may be important in vascular remodelling and the pressor response via autocrine and paracrine mechanisms. We evaluated the influences of ageing and β-adrenoceptor stimulation on the production of vascular Angll and eicosanoids in male spontaneously hypertensive rats (SHR), aged 5,17 and 30 weeks, and age-matched Wistar-Kyoto (WKY) rats. 2. All rats were weighed and their systolic blood pressure (SBP) was measured by the tail-cuff method. Mesenteric arteries were isolated and perfused with Krebs'-Henseleit solution. The outflows of prostaglandin E₂ (PGE₂), 6-keto-PGF_1α, thromboxane B₂ (TxB₂) and AngII were measured by specific radioimmunoassays. 3. The SBP was higher in SHR than in WKY rats in the 17-and 30-week-old groups and increased with age. Basal levels of PGE₂ were significantly lower in SHR than in WKY rats. The ratios of 6-keto-PGF_1α to TxB₂ and PGE₂ to TxB₂ were significantly lower in 17-week-old SHR compared with age-matched WKY rats. Basal Angll release did not differ between SHR and WKY rats and decreased with age. Isoproterenol stimulated the release of Angll; the magnitude of the increment was greater in WKY rats than in age-matched SHR. These results show that there is an imbalance in the production of vasodilator and vasoconstrictor eicosanoids in the resistance vessels of SHR at ages at which hypertension developed. 4. This imbalance may contribute to the increased vasoconstrictor response and vascular remodelling in SHR. Our findings suggest that vascular Angll plays a role in the ageing process and that β-adrenoceptor-stimuIated release of vascular Angll is impaired in SHR.     

Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats

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.     

Effect of cross-fostering on renal anti-oxidant/oxidant status and development of hypertension in spontaneously hypertensive rats

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.     

AGE-RELATED CHANGES IN NEUROPEPTIDE Y CONTENT IN BRAIN AND PERIPHERAL TISSUES OF SPONTANEOUSLY HYPERTENSIVE RATS

1. This study examined neuropeptide Y (NPY) concentrations in brain regions and peripheral tissues of young (3–4 months) and old (17–18 months) normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Neuropeptide Y-like immunoreactivity (NPY-LI) was determined in kidney, adrenal, heart ventricles, atria and four brain regions, cerebral cortex, hypothalamus, ventrolateral medulla (VLM) and dorsomedial medulla containing the nucleus tractus solitarius (NTS), by radio-immunoassay following acid extraction. 3. Significant age-related increases in organ weights were observed in atria, ventricle and kidney of both WKY and SHR (P<0.01). In order to take into account tissue hypertrophy, NPY-LI data were analysed as pmol/g tissue as well as total pmol/tissue. 4. At each age, similar NPY-LI concentrations were observed in WKY and SHR in all brain regions. A significant age-induced decrease in NPY-LI concentration and total NPY content was found in the hypothalamus of both WKY and SHR (P<0.01). 5. In the cardiac ventricle, decreases were observed in NPY-LI concentration with ageing, and in SHR relative to WKY; however, no differences were observed in total NPY-LI content. A significant age-related increase in adrenal NPY-LI concentration was observed. No age- or strain-related alterations in atrial or renal NPY-LI were detected, with the exception of an increase in total kidney NPY-LI in WKY with ageing. 6. Thus in the periphery, few changes in NPY-LI were observed with genetic hypertension or with ageing. A significant reduction in hypothalamic NPY-LI concentration occurred with age in both normotensive and hypertensive rats. Thus the previously reported age-related reduction in NPY-LI in the hypothalamus, an area where the peptide influences neuro-endocrine responses and food and water ingestion, is not affected by hypertension.     

Nitric oxide-dependent hypotensive effects of adrenomedullin in rats

The association of nitric oxide (NO) with the hypotensive effects of adrenomedullin (AM) was investigated in anesthetized rats. Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used at 11–13 weeks of age. Blood pressure and heart rate were measured from the femoral artery under mild anesthesia using pentobarbital. AM, over the dose range of 0.3–3 nmol/kg iv, produced dose-dependent sustained hypotension and compensatory tachycardia. These effects of AM at 0.3, 1, and 3 nmol/kg iv were significantly stronger in SHR (−9 ±4, −53 ±9, and −62 ±7 mmHg) than in WKY (−4 ±1, −16 ±2, and −22 ±2 mmHg). Those at 1 nmol/kg iv were markedly inhibited in SHR (−53 to −19 mmHg) and in WKY (−16 to −12 mmHg) by treatment with the nitric oxide synthase (NOS) inhibitor N^G-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv). On the other hand, the difference of hypotensive effects in WKY and SHR by calcitonin gene-related peptide (CGRP) and the inhibitory effect by the treatment with L-NAME were smaller than seen with AM. These effects of CGRP at 0.03, 0.1, 0.3, and 1 nmol/kg iv were in SHR (−7 ±2, −18 ±3, −42 ±4, and −74 ±3 mmHg) and in WKY (−7 ±1, −16 ±1, −26 ±3, and −41 ±2 mmHg), respectively. Those at 0.3 nmol/kg iv were not significantly inhibited in SHR (−42 to −43 mmHg) and in WKY (−26 to −20 mmHg) by treatment with L-NAME, 10 mg/kg iv. These results indicate that the AM hypotensive effect was more pronounced in the hypertensive state and strongly depends on NO synthesis. © 1996 Wiley-Liss, Inc.     

Pubertal administration of antiserum against nerve growth factor regresses renal vascular remodeling in spontaneously hypertensive rats

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.     

Antihypertensive activity of the aqueous extract of Retama raetam Forssk. leaves in spontaneously hypertensive rats

The antihypertensive and diuretic effects of the aqueous extract of Retama raetam Forssk. (RR) leaves were studied in both normotensive (WKY) and spontaneously hypertensive rats (SHR). In SHR rats, daily oral administration of RR (20 mg/kg) for three weeks exhibited a significant reduction in blood pressure. The systolic blood pressure decreased significantly from the seventh day (P < 0.01) and persisted through the end of treatment (P < 0.001) in SHR rats. The RR significantly enhanced the diuresis in WKY rats (P < 0.001). Furthermore, oral administration of RR at a dose of 20 mg/kg produced a significant increase on urinary excretion of sodium (P < 0.05), potassium (P < 0.01) and chlorides (P < 0.01) in SHR rats. In WKY rats, RR treatment induced a significant increase on urinary potassium elimination (P < 0.05) without affecting sodium and chloride excretion. Irbesartan (Avapro) 20 mg/kg (body weight), an angiotensin II receptor antagonist, was used as reference drug. No significant changes were noted in heart rate after RR treatment in SHR as well as in WKY rats. Glomerular filtration rate showed a significant increase after RR administration in WKY rats (P < 0.01) and a no significant increase in SHR rats. These results suggest that oral administration of aqueous RR extract exhibited antihypertensive and diuretic effects in SHR rats and diuretic action in WKY rats.     

Catecholaminergic and opioidergic mechanisms involved in the hypotensive response of pindolol

The present study evaluated the involvement of opioidergic and catecholaminergic mechanisms in the hypotensive action of pindolol. Pindolol (1 mg/kg i.a.) was administered to unanesthetized spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats instrumented for direct arterial pressure monitoring. Peripheral administration of pindolol produced a significant decrease in blood pressure in both SHR and WKY rats with SHR animals having a greater response. Heart rate was reduced in SHR; however, a tachycardia was observed in WKY rats. Pretreatment with naloxone (100 micrograms/kg i.a.) 10 min prior to pindolol administration prevented the hypotensive response. Similar pretreatment with yohimbine, an alpha 2-receptor antagonist, also prevented the pindolol-induced hypotensive response in both SHR and WKY rats. Neither naloxone nor yohimbine alone significantly affected blood pressure or heart rate. These results suggest that opioidergic and catecholaminergic mechanisms are involved in the hypotensive action of pindolol.     

缬沙坦对自发性高血压大鼠肾脏核因子-κB蛋白表达的影响

目的:探讨自发性高血压大鼠(SHR)肾组织NF-κB原位表达变化以及AT1受体阻断剂缬沙坦对其的影响。方法:16只SHR随机分成SHR组和SHR加缬沙坦药物干预组(1 mg.kg-1.d-1),另8只WKY大鼠为正常对照组。分别在实验第2、4、6、8周末测定大鼠尾动脉收缩压(SBP);实验结束取各组大鼠血浆测定血浆中肾素、血管紧张素II(AngII)水平;取出各组大鼠两侧肾脏组织,分别运用免疫组化原位测定肾组织中NF-κB蛋白表达,并进行半定量分析。结果:SHR组SBP和血浆中肾素活性以及AngII水平与WKY大鼠相比显著增高,缬沙坦治疗组SBP显著降低,但血浆中肾素活性以及AngII水平明显高于SHR组和WKY组。在蛋白水平,WKY组大鼠肾组织中NF-κB表达较低,SHR组肾小球和肾小管中NF-κB高度表达;使用缬沙坦干预后,NF-κB表达显著降低。结论:在蛋白水平对NF-κB表达的调控可能参与缬沙坦的降血压效应和肾保护作用。     

NERVE GROWTH FACTOR mRNA CONTENT PARALLELS ALTERED SYMPATHETIC INNERVATION IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. In order to explore the mechanisms responsible for the hypernoradrenergic innervation of the vasculature in the spontaneously hypertensive rat (SHR) the tissue content of nerve growth factor messenger ribonucleic acid (NGFmRNA) was examined. 2. The concentration of NGFmRNA was markedly elevated in mesenteric veins obtained from SHR when compared with the contents of NGFmRNA in veins from Wistar Kyoto rats (WKY). 3. The NGFmRNA content of kidneys was greater in SHR when compared with the levels present in WKY rats for 10- and 43-day-old animals. 4. In contrast to the pattern observed for veins and kidneys, the NGFmRNA content of SHR hearts was smaller than those present in hearts from WKY rats for 2, 10 and 43-day-old animals. 5. The results demonstrate that tissues with enhanced innervation (the kidney and mesenteric vasculature) in SHR are associated with an enhanced expression of NGFmRNA. In contrast, the heart, which does not display an enhanced sympathetic innervation in the SHR, does not have an increased expression of NGFmRNA. 6. It is suggested that in the SHR there is a tight relationship between hypernoradrenergic innervation in the vasculature and gene expression for NGFmRNA.