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大鼠高血压和衰老过程中血管β-肾上腺素能受体介导的反应

Vascular beta-adrenoceptor-mediated responses in hypertension and ageing in rats.

作者信息

Borkowski K R, Gros R, Schneider H

机构信息

Clinical Pharmacology Group, John P. Robarts Research Institute, London, Ontario, Canada.

出版信息

J Auton Pharmacol. 1992 Dec;12(6):389-401. doi: 10.1111/j.1474-8673.1992.tb00387.x.

Abstract
  1. In normotensive Wistar (W) and spontaneously hypertensive (SHR) rats between 5 and 20 weeks of age, there was an age-related increase in blood pressure (r2 = 0.770 and r2 = 0.801 respectively). Except for adrenaline (r2 = 0.979) in SHRs, plasma catecholamines and age were unrelated. 2. In ring segments of thoracic aorta from 5, 10, 15 and 20 week old rats, the respective EC80s (-log M) for phenylephrine (PE)-induced contractions were 8.20 +/- 0.37, 7.96 +/- 0.10, 7.15 +/- 0.12 and 7.12 +/- 0.21 in W and 7.73 +/- 0.13, 7.72 +/- 0.16, 7.37 +/- 0.08 and 7.40 +/- 0.03 in SHR tissues (means +/- SEM; n = 5-7). 3. In PE-preconstricted rings, the respective EC50s (-log M) for isoprenaline (IPNA)-induced relaxation were 7.97 +/- 0.11, 7.74 +/- 0.10, 6.96 +/- 0.19 and 6.57 +/- 0.26 in W and 8.03 +/- 0.24, 7.62 +/- 0.08, 6.88 +/- 0.13 and 6.73 +/- 0.14 in SHR tissues (n = 5-7). 4. In PE-preconstricted rings from 5 and 20 week old rats, a single concentration of IPNA (approximating the respective IPNA EC50s) induced relaxation which was sustained over 2 h in W but not SHR tissues. The SHR:W ratios of the net relaxant responses, at 5 and 20 weeks, were 0.6461 and 0.6167 respectively. 5. Thus, W rats exhibit an age-related loss in both vascular alpha- and beta-adrenoceptor responsiveness which appears unrelated to plasma catecholamines. SHRs also exhibit an age-related loss in vasodilator beta-adrenoceptor responsiveness, which may involve adrenaline-induced desensitization, but appear to maintain vasoconstrictor alpha-adrenoceptor responsiveness. It is proposed that an age-related decline in beta-adrenoceptor responsiveness coupled to maintenance of alpha-adrenoceptor responsiveness may lead to chronic blood pressure elevation, as observed in SHRs, while a parallel decline in both alpha- and beta-adrenoceptor responsiveness, as observed in W rats, may preclude hypertension development.
摘要
  1. 在5至20周龄的血压正常的Wistar(W)大鼠和自发性高血压(SHR)大鼠中,血压随年龄增长而升高(r2分别为0.770和0.801)。除了SHR大鼠中的肾上腺素(r2 = 0.979)外,血浆儿茶酚胺与年龄无关。2. 在5、10、15和20周龄大鼠的胸主动脉环段中,去氧肾上腺素(PE)诱导收缩的相应EC80s(-log M)在W大鼠中分别为8.20±0.37、7.96±0.10、7.15±0.12和7.12±0.21,在SHR组织中分别为7.73±0.13、7.72±0.16、7.37±0.08和7.40±0.03(均值±SEM;n = 5 - 7)。3. 在PE预收缩的血管环中,异丙肾上腺素(IPNA)诱导舒张的相应EC50s(-log M)在W大鼠中分别为7.97±0.11、7.74±0.10、6.96±0.19和6.57±0.26,在SHR组织中分别为8.03±0.24、7.62±0.08、6.88±0.13和6.73±0.14(n = 5 - 7)。4. 在5周龄和20周龄大鼠的PE预收缩血管环中,单一浓度的IPNA(接近各自的IPNA EC50s)诱导的舒张在W大鼠组织中可持续2小时以上,但在SHR组织中则不然。在5周龄和20周龄时,净舒张反应的SHR:W比值分别为0.6461和0.6167。5. 因此,W大鼠在血管α和β肾上腺素能受体反应性方面均表现出与年龄相关的丧失,这似乎与血浆儿茶酚胺无关。SHR大鼠在血管舒张β肾上腺素能受体反应性方面也表现出与年龄相关的丧失,这可能涉及肾上腺素诱导的脱敏,但似乎维持了血管收缩α肾上腺素能受体反应性。有人提出,与α肾上腺素能受体反应性维持相关的β肾上腺素能受体反应性的年龄相关下降可能导致慢性血压升高,如在SHR大鼠中观察到的那样,而在W大鼠中观察到的α和β肾上腺素能受体反应性的平行下降可能会阻止高血压的发展。

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