Exercise training attenuates hypertension progression via activation of central ACE2-Ang(1-7)-Mas axis in prehypertensive rats / 中国病理生理杂志

AIM:To investigate the effects of exercise training on the progression from prehypertension to hy -pertension,blood pressure regulation and the angiotensin-converting enzyme 2(ACE2)-angiotensin(Ang)(1-7)-MAS axis activation in cardiovascular centers ,and to elucidate the central mechanisms of exercise training postponing hyperten -sion progression.METHODS:The male spontaneously hypertensive rats(SHR;n=20,5 weeks old)and normotensive Wistar Kyoto(WKY)rats(n=20)were randomly assigned to sedentary(Sed)group and exercise training(ExT)group. The trained rats run on a treadmill in moderate-intensity for 20 weeks.Systolic blood pressure(SBP)was measured by tail-cuff method.The baroreflex sensitivity(BRS)was assessed by intravenous injection of phenylephrine.The expression of ACE2 and MAS receptor at mRNA and protein levels in baroreflex centers were determined by real-time PCR and Western blot,respectively.Alterations of BRS were evaluated before and after intracerebroventricular injection of MAS receptor ago -nist Ang(1-7)and its antagonist A779,respectively.RESULTS:Compared with SHR +Sed group,exercise training since prehypertension significantly postponed the development of hypertension ,delayed the hypertension progression ,and decreased SBP in both SHR and WKY rats(P<0.05).Exercise training enhanced blood pressure regulation and improved the BRS in SHR(P<0.01).The expression of ACE2 and MAS receptor at mRNA and protein levels in the baroreflex cen-ters(rostral ventrolateral medulla ,nucleus tract solitarius and paraventricular nucleus )were up-regulated in SHR +ExT group(P<0.05).Central administration of A779 abolished the benefits of exercise-induced improvement of BRS in SHR +ExT group(P<0.01).In contrast,Ang(1-7)improved the BRS in both SHR +Sed group and SHR +ExT group(P<0.05).CONCLUSION:Exercise training postpones hypertension progression and improves blood pressure regula -tion,which may be associated with the activation of central ACE 2-Ang(1-7)-Mas axis.

Central oxidative stress depresses baroreflex function in spontaneously hypertensive rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of central oxidative stress on the baroreflex function and central mechanism responsible for the attenuated baroreflex sensitivity (BRS) in spontaneously hypertensive rats (SHR).</p><p><b>METHODS</b>Male 24-week-old SHR and normal rats were anesthetized with urethane and alpha-chloralose. Intravenous injection of phenylephrine (PE) and sodium nitroprusside (NP) evoked arterial baroreflex. The ratio of change in heart rate (HR) to change in mean aortic pressure (MAP) represented the baroreflex sensitivity (BRS). Alteration in BRS was evaluated before and after intracerebroventricular administration of superoxide dismutase (SOD) mimetic tempol or SOD inhibitor diethyldithiocarbamic acid (DETC).</p><p><b>RESULTS</b>BRS in hypertensive rats was significantly lower than that in normal rats (PE: P < 0.01, NP: P < 0.01). Intracerebroventricular administration of Tempol significantly improved BRS in hypertensive rats (P < 0.05), but not in normal rats. In contrast, DETC decreased BRS to a greater extent in normal group than in hypertension group (P < 0.05). MDA content in hypothalamus of hypertensive rats was higher than that of normal rats (P < 0.01), whereas total antioxidant capacity, total SOD, CuZn-SOD, catalase activity were lower in hypertensive rats than in normal rats (P < 0.05).</p><p><b>CONCLUSION</b>Attenuated baroreflex function in hypertensive rats is associated with central oxidative stress, which is linked to decreases in antioxidant enzyme activity and antioxidative capacity in the brain.</p>

Preventive effect of endothelin-1 pretreatment on hypoxia-induced injury in cultured neonatal rat cardiomyocytes / 生理学报

This study was designed to observe the effects of endothelin-1 (ET-1) pretreatment on hypoxia-induced injury and changes in [Ca(2+)](i) in cultured neonatal rat cardiomyocytes. The activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD), and the content of malondialdehyde (MDA) in the supernatant were determined in the cultured cardiomyocytes subjected to a 12-h hypoxia induced by a 3% O(2)-5% CO(2) atmosphere at 37 with or without ET-1 pretreatment. [Ca(2+)](i) was measured with Ca(2+)-sensitive fluorescent probe fluo-3/AM under a laser scanning confocal microscope. Fluorescence intensity emitted from fluo-3/AM-loaded cells reflected the concentration of [Ca(2+)](i). The hypoxia model used in [Ca(2+)](i) measurement was established by continously perfusing cardiomyocytes for 30 min with 95% N(2)-5% CO(2) saturated DMEM solution containing 1 mmol/L Na(2)S(2)O(4). Pretreatment with ET-1 consisted of three cycles of ET-1 perfusion (5 min for each) followed by ET-1-free DMEM solution (10 min for each) prior to hypoxia. The results showed that (1) after incubation in a 3% O(2)-5% CO(2) hypoxic atmosphere for 12 h, the activity of LDH and the content of MDA in the supernatant significantly increased from 19.33+/-1.03 U/L to 43.33+/-1.21 U/L and from 0.91+/-0.03 nmol/L to 1.71+/-0.02 nmol/L, respectively, whereas the activity of SOD decreased from 33.48+/-1.15 U/ml to 16.93+/-1.11 U/ml (P<0.01). In hypoxic cardiomyocytes pretreated with 0.01-1 nmol/L ET-1, LDH release and supernatant MDA content were decreased, while SOD activity was enhanced dose-dependently (P<0.01). (2) The spontaneous calcium transient in cultured cardiomyocytes terminated at 29+/-1.5 s and [Ca(2+)](i) increased by 107+/-13.2% during perfusion of hypoxic solution (P<0.001) at the end of 30 min. ET-1 (0.01-1 nmol/L) increased the frequency of [Ca(2+)](i) transient in cultured cardiomyocytes in a dose-dependent manner (P<0.01). The termination of [Ca(2+)](i) transient and the elevation of [Ca(2+)](i) caused by hypoxia were postponed by pretreatment with 0.01-1 nmol/L ET-1 (P<0.01). These results show that pretreatment with 0.01-1 nmol/L ET-1 attenuates hypoxia-induced injury and [Ca(2+)](i) changes in cultured neonatal cardiomyocytes, indicating a cyto-protective role of ET-1 pretreatment.