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拉贝洛尔对大鼠肾皮质切片肾素释放的影响。

Effects of labetalol on renin release from rat kidney cortical slices.

作者信息

Morimoto S, Matsumura Y

出版信息

J Pharmacobiodyn. 1986 Nov;9(11):928-33. doi: 10.1248/bpb1978.9.928.

Abstract

Effects of labetalol, a combined alpha- and beta-adrenoceptor blocking agent, on the changes in renin release in response to isoproterenol or norepinephrine were examined in comparison with those of propranolol and prazosin, using rat kidney cortical slices. Isoproterenol (10(-9) to 10(-5) M) produced a dose-related increasing effect on renin release from the slices, although the increased release was markedly attenuated by the higher dose (10(-4) M). On the other hand, norepinephrine, at relatively higher concentrations (over 10(-6) M), caused a significant decreasing action on the release. Labetalol alone (10(-9) to 10(-4) M) had no effect on basal renin release. However, the agent exerted a concentration-dependent blocking action on the renin response to 10(-6) M isoproterenol. Similar results were observed with propranolol. The decreased response of renin release to 10(-5) M norepinephrine was significantly inhibited by labetalol over 10(-6) M. Labetalol, at a concentration of 10(-5) M, abolished the decreased release by 10(-5) M norepinephrine. On the other hand, the decreasing effect of 10(-5) M norepinephrine was substantially reversed rather than abolished by prazosin over 10(-7) M. These results indicate that labetalol inhibited the response of renin in rat kidney cortical slices, by beta- and alpha 1-adrenoceptor antagonistic action, respectively.

摘要

使用大鼠肾皮质切片,将α、β肾上腺素受体阻断剂拉贝洛尔与普萘洛尔和哌唑嗪相比较,研究其对异丙肾上腺素或去甲肾上腺素引起的肾素释放变化的影响。异丙肾上腺素(10⁻⁹至10⁻⁵M)对切片肾素释放产生剂量相关的增加作用,尽管较高剂量(10⁻⁴M)时增加的释放明显减弱。另一方面,去甲肾上腺素在相对较高浓度(超过10⁻⁶M)时对释放产生显著的减少作用。单独使用拉贝洛尔(10⁻⁹至10⁻⁴M)对基础肾素释放无影响。然而,该药物对肾素对10⁻⁶M异丙肾上腺素的反应发挥浓度依赖性阻断作用。普萘洛尔也观察到类似结果。拉贝洛尔超过10⁻⁶M可显著抑制肾素对10⁻⁵M去甲肾上腺素释放反应的降低。拉贝洛尔浓度为10⁻⁵M时,可消除10⁻⁵M去甲肾上腺素引起的释放减少。另一方面,10⁻⁵M去甲肾上腺素的减少作用在哌唑嗪超过10⁻⁷M时基本逆转而非消除。这些结果表明,拉贝洛尔分别通过β和α₁肾上腺素受体拮抗作用抑制大鼠肾皮质切片中肾素的反应。

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