Activities of hypothalamic angiotensin II-sensitive neurons are greately enhanced even in prehypertensive spontaneously hypertensive rats

We have previously demonstrated that some neurons in the anterior hypothalamic area (AHA) of rats are tonically activated by endogenous angiotensins and that reactivities of these neurons to angiotensin II are enhanced in 15- to 16-week-old spontaneously hypertensive rats (SHR). To investigate whether the enhanced reactivity of SHR AHA neurons to angiotensin II is secondary to raised blood pressure, we examined whether the enhanced reactivity to angiotensin II also occurs in prehypertensive SHR. We also examined whether reactivities of AHA angiotensin II-sensitive neurons to intracerebroventricular hypertonic saline are enhanced in prehypertensive SHR, since intracerebroventricular injection of hypertonic saline increases the firing rate of AHA neurons via release of angiotensins at AHA neuron levels. Male 4-week-old SHR and age-matched Wistar Kyoto rats (WKY) were used in this study. There was no difference in systolic blood pressure between both rats. They were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Pressure application of angiotensin II onto some AHA neurons increased their firing rate. The basal firing rate of angiotensin II-sensitive neurons was increased in SHR as compared with WKY. The increase of unit firing by angiotenisn II was enhanced in SHR as compared with WKY. Intracerebroventricular injection of hypertonic saline increased the firing rate of AHA angiotensin II-sensitive neurons. The average threshold sodium concentration for the saline-induced increase of neural firing was lower in SHR than in WKY. These findings demonstrate that basal activities and responsiveness to angiotensin II in AHA angiotensin II-sensitive neurons are enhanced in prehypertensive SHR as compared with age-matched WKY. In addition, these findings indicate that central saline-induced activation of AHA angiotensin II-sensitive neurons is also enhanced in SHR. It appears that the enhanced reactivity of SHR AHA neurons to angiotensin II occurs primarily in nature but not secondarily to raised blood pressure in SHR.     

Effects of ageing on cardiac performance and coronary flow in spontaneously hypertensive and normotensive rats

The aim of the present study was to assess the influence of ageing on cardiac function and coronary flow in Wistar Kyoto normotensive rats (WKY, 16 and 78 weeks of age) and spontaneously hypertensive rats (SHR) of the same age. Cardiac function was determined on isolated hearts by means of an antegrade heart perfusion technique. Left atrial pressure and peak aortic pressure could be altered independently of each other. Recordings of cardiac output and coronary flow were then obtained at both normotensive and hypertensive levels of peak aortic pressures. Peak stroke volume (SV) was reduced with age in both WKY and SHR. Peak SV determined at normotensive pressure loads became diminished with age in WKY, while it at hypertensive pressure loads showed a small decline with age, since peak SV was low as early as 16 weeks of age. The age-dependent fall in cardiac performance was greater in SHR than in WKY, due to the enhanced peak SV in 16-week-old SHR at hypertensive pressure loads. Peak SV was markedly decreased at normotensive pressure levels in both 16- and 78-week-old SHR v. age-matched WKY. Coronary flow per unit tissue declined with age both in WKY and SHR. Coronary flow was also lower in SHR compared to age-matched WKY. With ageing this elevated performance was reduced down to the same level as in 78-week-old WKY. The age-related coronary flow reduction and the consistently reduced flow in SHR indicate a structural narrowing of the coronary vascular bed, particularly in SHR.     

Angiotensin II sensitivity of anterior hypothalamic area neurons is enhanced in both spontaneously hypertensive rats and Dahl salt-sensitive rats

We have previously demonstrated that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins. Furthermore, we have demonstrated that intracerebroventricular injection of hypertonic saline increases the firing rate of AHA angiotensin II-sensitive neurons via angiotensins and that the central sodium-induced activation of AHA neurons is enhanced in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (Dahl S) rats. In this study, we examined whether sensitivities of AHA angiotensin II-sensitive neurons to angiotensin II are enhanced in SHR and Dahl S rats as compared with their respective controls. Male 15- to 16-week-old SHR and age-matched Wistar Kyoto rats (WKY), and male 15- to 16-week-old Dahl S rats and Dahl R rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. In SHR, pressure application of angiotensin II (3 x 10(-9) to 3 x 10(-8) M) onto AHA angiotensin II-sensitive neurons increased their firing rate in a concentration-dependent manner. In WKY, only the highest concentration of angiotensin II increased the firing rate, while the lower concentrations of angiotensin II did not affect it. In Dahl S rats, pressure application of angiotensin II (10(-8) and 3 x 10(-8) M) onto AHA neurons increased their firing rate, while angiotensin II (3 x 10(-9) M) did not affect it. In Dahl R rats, the highest concentration of angiotensin II increased the firing rate, while the lower concentrations of angiotensin II did not affect it. These findings indicate that the sensitivity of AHA neurons to angiotenisn II is enhanced in SHR and Dahl S rats as compared with their respective controls.     

Alterations in tissue concentration and gene expression of adrenomedullin in spontaneously hypertensive rats

In order to elucidate the role of adrenomedullin in hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of 8-week-old spontaneously hypertensive rats (SHR) with those of age-matched Wistar-Kyoto rats (WKY). The adrenomedullin immunoreactivity concentrations in adrenal gland and cardiac atrium were significantly higher in SHR than in WKY. The adrenomedullin content of cardiac ventricle was also significantly higher in SHR than in WKY. The rat adrenomedullin messenger RNA levels in adrenal gland and heart of SHR were also higher than those of WKY. These results suggest that adrenomedullin participates in the mechanism to counteract the blood pressure elevation in SHR.     

短链酰基辅酶A脱氢酶在大鼠心脏发育中的表达及其与心肌肥厚的关系

 目的：研究大鼠心脏发育过程中短链酰基辅酶A脱氢酶(short-chain acyl-CoA dehydrogenase, SCAD)的表达变化规律,并探讨其与高血压大鼠心肌肥厚的关系。方法：观察不同时期Wistar大鼠和不同周龄自发性高血压大鼠心肌组织的SCAD蛋白表达及酶活性变化,检测大鼠的血清和心肌游离脂肪酸含量。结果：与胚胎期19 d Wistar大鼠组比较,出生后1 d、2周、6周及16周龄Wistar大鼠组心肌的SCAD蛋白表达及酶活性增加,血清和心肌游离脂肪酸含量明显减少,二者之间呈负相关,其中,从2周龄Wistar大鼠组开始差异有统计学意义。与周龄匹配的WKY大鼠组比较,2周龄自发性高血压大鼠组收缩压尚未升高,6周龄及16周龄自发性高血压大鼠组收缩压显著增高;各时点自发性高血压大鼠组的左室重量指数均明显增高,提示自发性高血压大鼠在血压升高之前,已经发生了明显的心肌肥厚。与周龄匹配的WKY大鼠组比较,2周、6周及16周龄自发性高血压大鼠组心肌的SCAD蛋白表达及酶活性明显下降,血清和心肌游离脂肪酸含量明显增加,呈显著负相关。结论：(1)SCAD蛋白表达随大鼠心脏的生长发育逐渐上调,可能与心脏对脂肪酸的利用增加密切相关。(2)SCAD的蛋白表达及其酶活性显著下降, 可能是导致自发性高血压大鼠肥厚心肌能量代谢“胚胎型再演”的分子基础。     

Renal sodium excretion after oral or intravenous sodium loading in sodium-deprived normotensive and spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats that had been on a low sodium diet for 3 days were given 1.5 mmol sodium chloride kg^-1 body weight either orally or intravenously. The rats receiving an oral sodium load showed a greater natriuresis than those receiving the same saline load intravenously. No increase of renal sodium excretion was observed when the rats received a hypertonic mannitol solution orally. The cumulative sodium excretion during the 8 h following oral loading was two to three times larger in SHR than in WKY, whereas no difference between strains could be demonstrated after giving saline intravenously. Furthermore, after switching from normal to low sodium diet the rate of decrease of renal sodium excretion was greater in SHR than in WKY rats. It is proposed that there exists a gastrointestinal sensory mechanism for sodium controlling the renal sodium excretion. Furthermore, it is suggested that the function of this mechanism differs between SHR and WKY.     

不同年龄高血压大鼠血管平滑肌中ERK和MKP-1的表达

目的：研究不同年龄的自发性高血压大鼠（SHR）和Wistar Kyoto大鼠（WKY）主动脉平滑肌中丝裂原活化蛋白激酶（MAPK）及其磷酸酶（MKP-1）的表达及其与高血压的关系。 方法： 用tail-cuff测量大鼠尾动脉血压；分别用Western blotting法和RT-PCR法半定量测定血管平滑肌中磷酸化细胞外信号调节激酶（p-ERK）和MKP-1的蛋白表达以及MKP-1 mRNA的含量。 结果： （1）SHR的血压自8周龄起明显高于WKY（P<0.01），且随年龄增长而升高（P<0.05）至14周以后趋于稳定；（2）SHR主动脉平滑肌中的p-ERK表达明显高于同年龄的WKY（P<0.01），随年龄增长而递增（P<0.05），与血压呈正相关；（3）SHR主动脉平滑肌中MKP-1蛋白明显高于同龄WKY，而mRNA的表达在5周龄时明显高于WKY，之后均随年龄的增长而递减（P<0.05），与血压和ERK呈负相关，而WKY下降不明显。 结论： MKP-1在高血压的发生和发展过程中起重要作用，其表达逐渐下降可能是导致ERK激活增加，从而导致血管平滑肌细胞增殖、血压升高的重要原因。     

Lipid peroxidation and myocardial vulnerability in hypertrophied SHR myocardium.

In a comparison using age-matched Wistar-Kyoto rats (WKY), 16-week-old male spontaneously hypertensive rat (SHR) hearts were examined histologically and biochemically on the first and fourth day after administration of 20 mg/kg doxorubicin in order to examine whether membrane abnormalities in hypertrophied SHR myocardium are caused by lipid peroxidation. Morphological examination of the SHR revealed focal myocytolysis on the first day and severe cardiomyopathy involving diffuse myocytolysis and vacuolar degeneration in the left ventricle on the fourth day. The activity of a membrane-related enzyme, Na+/K(+)-ATPase, was already lower in control SHR than that of control WKY and was lower in both SHR and WKY than in the respective saline groups on the first day after administration, whereas the enzyme activity in the doxorubicin-treated SHR was not significantly different from that of the treated WKY. A thiobarbituric acid-reactant substance, a lipid peroxidation marker, was significantly higher in treated SHR than it was in the treated WKY on the first day. Furthermore, in comparison with WKY, alpha-tocopherol in the left ventricle in SHR was significantly lower on the fourth day after administration. These results show that a proneness to lipid peroxidation in the membrane system is closely associated with severity of doxorubicin-induced cardiomyopathy in SHR and suggests that membrane lipid peroxidation may cause a higher degree of vulnerability in hypertrophied SHR myocardium.     

Migration of vascular smooth muscle cells is enhanced in cultures derived from spontaneously hypertensive rat

 Migration of vascular smooth muscle cells (SMC) constitutes a common step in neointimal formation which occurs in several vascular diseases. Whether the migratory response of SMC derived from hypertensive animals is different to that of controls may provide a clue to the link between hypertension and atherosclerosis. We examined the migratory responses of SMC from cell cultures and ring explants (thin aortic ring segment) and compared these responses between normotensive and hypertensive rats at two different ages. Both scrape-wound assay and transwell chambers from cultured aortic SMC as well as aortic ring explant cell outgrowth models were employed. The aortae were obtained from male spontaneously hypertensive rats (SHR) and their normotensive counterpart the Wistar-Kyoto rat (WKY) at 5 and 20 weeks of age. Migration was induced by fetal bovine serum or platelet-derived growth factor (PDGF) and migrated cells were counted at different times following stimulation. We found that SMC migration exhibited a high sensitivity to serum (range of ED₅₀: 2.2–3.6%), migration of SMC from 20-week-old SHR exceeded (by 46%, P<0.025) that of SMC from age-matched WKY and the difference became significant as early as 8 h after stimulation by serum. Chemotaxis induced by PDGF (2 h) exhibited similar differences. An elevated migratory response in SHR-SMC was also found in cells derived from 5-week-old rats in whom the blood pressure was normal. In younger animals, cell outgrowth from SHR aortic ring explants also accumulated more cells compared with WKY without a higher growth rate, thus suggesting that SHR-SMC have a higher migratory response ex vivo. In conclusion, aortic SMC migration appeared to be enhanced in various preparations from SHR. This difference also existed in young animals before the elevation of blood pressure occurred and might contribute partly to the role of hypertension as a risk factor for atherosclerosis. Received: 2 April 1997 / Received after revision: 2 September 1997 / Accepted: 8 September 1997     

Influence of circadian time, ageing, and hypertension on the urinary excretion of nitric oxide metabolites in rats

Urinary excretion of NO metabolites (NOx) was measured in male spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY) in two age groups: young (11 weeks) and old (58 weeks). Urine was collected every 6 h throughout 24 h with and without injection interperitoneally of N(G)-nitro-L-arginine-methyl-ester (L-NAME), 30 mg/kg, at 7:00 or 19:00 h. In addition, blood pressure changes by L-NAME were evaluated using radiotelemetry. In both strains of rats, injection of L-NAME abolished almost completely the urinary excretion of NOx, indicating that urinary NOx indeed reflect the endogenous rate of NO synthesis. Time-dependent variation in urinary NOx excretion was observed in WKY rats of both ages (analysis of variance, P<0.05), with higher excretion in the dark period. In SHR rats, time-dependent variation in NOx excretion was lost, and the overall amount of NOx excreted within 24 h was significantly lower in young SHR than in age-matched WKY rats. Moreover, blood pressure increases by L-NAME were significantly smaller in SHR than in WKY rats. In old rats of both strains, NOx excretion was reduced, and the difference between the strains disappeared. Our findings demonstrate that ageing is accompanied by a loss in NOx excretion, and suggest that hypertension in SHR leads to a reduction in NO synthesis already at young age.     

Factors affecting the acute pressor response to bolus cadmium injections

Cadmium chloride solutions were given at dosages of 1 or 2 mg/kg intraperitoneally, intravenously, subcutaneously or orally to conscious or anesthetized female rats. A rapid and persistent pressor response was usually obtained from parenteral, but not from oral administration. Blood pressure elevation was quantitatively equivalent at 15 and 30 min after injection, except on subcutaneous administration, in conscious and anesthetized rats, although anesthesia depressed the initial pressures. Within a minute or so of administration, all animals given cadmium intraperitoneally exhibited body, limb and tail movements typically displayed during parturition, and did so for up to two hours thereafter. When 5-week-old males of Sprague-Dawley, Fischer 344, SHR and WKY strains were given 2 mg/kg of CdCl₂ intraperitoneally, a pressor response did not usually occur. At 6–10 weeks of age a pressor response commonly occurred in conscious or unconscious Sprague-Dawley and Fischer 344, but only in unconscious SHR or WKY rats. Conscious males exhibited the same contortions as females following intraperitoneal cadmium injections.     

Cardiovascular concomitants of tactile and acoustic startle responses in spontaneously hypertensive and normotensive rats

In the present study we have simultaneously investigated cardiovascular and behavioral responses to repeated tactile and acoustic stimulation in adult, male, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Blood pressure and heart rate responses were increased in SHR vs. WKY rats following both types of stimuli. The pressor responses, but not the tachycardic responses, habituated with repeated stimulation in both strains and with both stimulus modalities. The rates of habituation were not significantly different between the two strains. Magnitudes of the behavioral startle responses were significantly elevated in SHR vs. WKY rats with tactile, but not with acoustic stimulation. No significant differences were found between the two strains with respect to the latency, with which the startle responses occurred. These data indicate that SHR as compared to WKY rats respond to repeated stimulation with two different stimulus modalities (tactile and acoustic) with significantly increased pressor and tachycardic responses. This cardiovascular hyperreactivity is not due to different degrees of habituation between the two strains and can be observed even in the absence of significant differences in standard behavioral startle response measures.     

Gαq/11介导的信号转导通路在自发性高血压大鼠主动脉中的变化

目的:观察自发性高血压大鼠 (SHR)主动脉Gαq/11及磷脂酶C(PLC)的动态变化,探讨其在SHR高血压发病机制中的意义。方法:4周龄和12周龄SHR,颈动脉插管记录动脉血压,放免法测定血浆血管紧张素Ⅱ的浓度,免疫印迹法检测主动脉组织Gαq/11和PLC的含量。结果:SHR12周龄时动脉血压明显增高。4周龄SHR主动脉Gαq/11的表达较对照高 69.2 % (P <0.05)。4周龄和12周龄SHR主动脉PLCβ₃分别较各自同龄对照组高66.9%和 85.1% (P <0.05)。结论:Gαq/11介导的信号转导通路上调参与SHR高血压的发生和发展.     

Nocturnal food-related hyperdipsia in the adult spontaneously hypertensive rat

Male adult spontaneously hypertensive rats (SHR) ate the same but drank more and had a higher water to food ratio (W:F) than did Wistar-Kyoto (WKY) rats in 24-hr when they had continuous access to standard laboratory pellets and tap water. When rats ate in the day phase of a 12:12 light/dark cycle after 24-hr food deprivation, SHR rats ate and drank the same as did WKY rats in a 60-min test. When the same rats ate at night after 24-hr food deprivation, however, SHR rats were hyperdipsic: They ate the same as did WKY rats, but SHR rats drank more and had a higher W:F. This relative hyperdipsia reflected the increased ability of ingestion of food to stimulate drinking in SHR, because when food was absent for a 60-min test at night SHR drank the same as did WKY rats. Three dipsogens which are candidate components for eating-elicited drinking in the rat, cellular dehydration, histamine and angiotensin II, elicited drinking differentially in SHR and WKY rats: SHR drank more than did WKY rats in response to (1) cellular dehydration produced by IP hypertonic saline, (2) large doses of SC histamine, and (3) SC angiotensin II. These results demonstrate that SHR exhibit a nocturnal food-related hyperdipsia which may reflect differential sensitivity to stimuli important for eating-elicited drinking such as increased osmolality and endogenous histamine or angiotensin.     

Evidence for a dissociation between cardiovascular and behavioral reactivity in the spontaneously hypertensive rat

Spontaneously hypertensive rats of the Okamoto strain (SHR) were compared with normotensive rats of the Wistar-Kyoto strain (WKY) on the acoustic startle response in rats prepared for simultaneous blood pressure recordings. Blood pressure was continuously recorded by means of an indwelling cannula in the caudal tail artery. The presentation of the startle stimulus caused a blood pressure response in both strains consisting of an initial increase in blood pressure followed by a decrease and after that a longer lasting, but less pronounced second increase in pressure. The startle-elicited increase in blood pressure was significantly elevated in SHRs and at the same time the acoustic startle response was depressed as compared to WKY rats. These data indicate a dissociation between cardiovascular and behavioral reactivity in the SHR.     

RNA阵列技术检测自发性高血压大鼠肌浆网Ca2+-ATP酶和受磷蛋白基因表达

目的:探讨肌浆网Ca²⁺-ATP酶(SERCA)和受磷蛋白(PLB)在原发性高血压发病过程中的变化特点及其相互关系。方法:提取2、4、6、8、10、12不同周龄雄性自发性高血压大鼠(SHR)和正常血压大鼠(WKY)的心室肌、血管平滑肌、肝脏和肾脏组织的总RNA,共294个样品,利用高通量RNA阵列技术(RNAarray)检测SERCA和PLB基因在不同周龄SHR和WKY中mRNA表达谱改变。结果:SHR在6、8、10、12周龄血压出现显著高于同周龄WKY(均P<0.01),10、12周龄心室肌重量／体重比出现显著增加(均P<0.01),心肌和血管平滑肌SERCA的表达在4、6、8、10、12周龄出现显著高于同周龄WKY(P<0.05或P<0.01)。PLB基因表达在两组间无显著差异(P>0.05)。心肌的SERCA与PLB表达量比值在6、8、10、12周龄出现显著大于同周龄WKY(P<0.05或P<0.01),而血管平滑肌的SERCA与PLB表达量比值在4、6、8、10、12周龄出现显著大于同周龄WKY(P<0.05或P<0.01)。结论:肌浆网SERCAmRNA表达改变及SERCA与PLB比例失常是高血压发生和发展过程中重要的分子生物学机制。     

Aging impairs the protective effect of magnesium supplementation on hypertension in spontaneously hypertensive rats.

Preeclampsia is a hypertensive disorder that is unique to pregnancy. Magnesium (Mg2+) supplementation is a potential new therapy to ameliorate development of hypertension. The aim of this work was to compare the effects of Mg2+ supplementation on systolic blood pressure (SBP) in young and aged rats. Spontaneously hypertensive rats (SHR) were divided into young (6-week-old male, n = 10) and old (16-week-old male, n = 10) groups. Each group of rats comprised two subgroups made of a control subgroup fed with normal rat chow (0.2% Mg2+, n = 5) and a high Mg2+ subgroup nourished with a Mg2+ rich diet (0.8% Mg2+, n = 5). Age-matched Wistar-Kyoto rats (WKY) were also allocated into two groups. SBP was assessed weekly for 12 weeks indirectly by the tail-cuff method. SBP increased progressively in SHR-young rats after 7 weeks. This increase was greater in the control subgroup compared to high Mg2+ subgroup at 7 weeks (p < 0.05). No difference in the SBP was registered between old SHR subgroups. Mg2+ supplementation does not exert antihypertensive effects in the WKY rats. In conclusion, Mg2+ supplementation may provide beneficial effect in the developmental phase of hypertension but not in established hypertension.     

Pathophysiologic role of natriuretic peptides

To evaluate the pathophysiologic role of atrial natriuretic peptide (ANP) in hypertension, hemodynamic effects of human ANP and antiserum against rat ANP were investigated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous administration of human ANP caused greater hypotension associated with a decrease of cardiac output in SHR than in WKY, which suggests that SHR have enhanced responsiveness to exogenous ANP. The antiserum increased blood pressure and cardiac output, with the latter being significantly greater in SHR than in WKY. These results suggest that endogenous ANP counteract, in part, the maintenance of hypertension. In addition, hemodynamic and renal excretory effects of brain natriuretic peptide (BNP), a novel natriuretic peptide identified from porcine, were studied in SHR and WKY. BNP caused marked natriuresis and hypotension in a dose-dependent fashion, as observed with ANP. Not only ANP but also BNP may have a role in the regulation of blood pressure and water-electrolyte balance.     

Influence of neonatal handling on blood pressure,locomotor activity,and preweanling heart rate in spontaneously hypertensive and Wistar Kyoto rats

This experiment tested the hypothesis that increased stimulation early in development would (a) alter developmental changes in heart rate and behavioral reactivity and (b) affect the level at which blood pressure was regulated in adulthood. For this purpose, the effects of daily handling and maternal separation (3 min per day) on both behavioral and cardiovascular measures were examined in spontaneously hypertensive (SHR) and normotensive control Wistar Kyoto (WKY) rats. Prior to weaning, elevated heart rates in pups handled during the first postnatal week were most pronounced among 4-week-old prehypertensive SHR pups. Early handling affected behavior observed during openfield testing similarly in young adult rats of the SHR and WKY strains (e.g., increased locomotor activity on the first day of testing). In female rats of the WKY strain, early handling resulted in a lower baseline blood pressure; the blood pressure; the blood pressure of SHR rats was not affected by increased stimulation in infancy. Examination of longitudinal data yielded no support for a direct association between behavioral reactivity or preweaning heart rate and high blood pressure. These findings demonstrate the influence of both early environmental conditions and genetic factors on maturation within the cardiovascular system and suggest that genetic models of pathological conditions may provide a productive means of examining environmentally shaped aspects of individual differences in physiological regulation.     

运动训练激活中枢ACE2-Ang(1-7)-MAS轴延缓高血压进展

目的:观察运动训练对高血压前期的血压进展、血压调节以及中枢血管紧张素转换酶2(ACE2)-血管紧张素(Ang)(1-7)-MAS轴的影响,探讨运动训练延缓高血压进展的中枢机制。方法:5周龄雄性自发性高血压大鼠(SHR)和正常血压WKY大鼠各20只,随机分成安静组和运动训练组,每组10只。运动组大鼠进行20周中低强度跑台运动。采用尾套法测定大鼠尾动脉收缩压,药物法检测动脉压力反射敏感性(BRS)。Real-time PCR和Western blot分别检测压力反射中枢ACE2和MAS的mRNA和蛋白表达。侧脑室注射MAS受体激动剂Ang(1-7)及拮抗剂A779,检测注药前后的BRS变化。结果:始于高血压前期的运动训练可推迟高血压发生、延缓高血压进展,明显降低SHR和WKY大鼠血压(P0.05),并改善SHR血压调节功能,提高其BRS(P0.01);此处,运动训练可上调SHR压力反射中枢(孤束核、延髓头端腹外侧区和室旁核中)ACE2和MAS的mRNA和蛋白表达(P0.05);中枢给予A779抵消了运动对SHR BRS的改善作用(P0.01),相反,注射Ang(1-7)则增强安静组和运动组SHR的BRS(P0.05)。结论:运动训练延缓高血压前期进展到高血压的进程及改善血压调节作用可能与运动增强中枢ACE2-Ang(1-7)-MAS轴功能有关。