普萘洛尔对大鼠肠系膜动脉床中α-肾上腺素受体介导的血管收缩具有立体选择性抑制作用。

Propranolol stereoselectively inhibits alpha-adrenoceptor-mediated vasoconstriction in mesenteric arterial beds of rats.

Stauber R E, Heinemann A

Department of Medicine, Karl Franzens University, Graz, Austria.

J Auton Pharmacol. 1996 Jun;16(3):125-9.

Abstract

The optical isomers of propranolol were compared for their effects on pressor responses to adrenergic and non-adrenergic vasoconstrictors in mesenteric arterial beds of rats. 2. R(+)-propranolol (10(-7)-10(-5) M) had no effect on vessel preparations stimulated with noradrenaline, methoxamine, or arginine-vasopressin. 3. S(-)-propranolol 10(-7) M did not alter pressor responses to noradrenaline. However, S(-)-propranolol 10(-6) and 10(-5) M inhibited vasoconstriction induced by noradrenaline. This effect was similar in the presence of indomethacin 3 x 10(-6) M. 4. S(-)-propranolol 10(-5) M also inhibited vasoconstriction induced by methoxamine, shifting the dose-response curves to the right, but did not affect pressor responses to arginine-vasopressin. 5. Schild analysis for equilibrium vasoconstrictor responses to methoxamine indicated stereoselective competitive alpha-adrenoceptor antagonism by propranolol. 6. These data suggest selective inhibition of alpha-adrenoceptor-mediated vasoconstriction by S(-)-propranolol at higher concentrations by competitive alpha-adrenoceptor antagonism.

摘要

比较了普萘洛尔的光学异构体对大鼠肠系膜动脉床中肾上腺素能和非肾上腺素能血管收缩剂升压反应的影响。2. R(+)-普萘洛尔（10(-7)-10(-5) M）对用去甲肾上腺素、甲氧明或精氨酸加压素刺激的血管制剂无影响。3. 10(-7) M的S(-)-普萘洛尔不改变对去甲肾上腺素的升压反应。然而，10(-6)和10(-5) M的S(-)-普萘洛尔抑制去甲肾上腺素诱导的血管收缩。在存在3×10(-6) M吲哚美辛的情况下，这种作用相似。4. 10(-5) M的S(-)-普萘洛尔也抑制甲氧明诱导的血管收缩，使剂量-反应曲线右移，但不影响对精氨酸加压素的升压反应。5. 对甲氧明平衡血管收缩反应的希尔德分析表明普萘洛尔具有立体选择性竞争性α-肾上腺素能受体拮抗作用。6. 这些数据表明，在较高浓度下，S(-)-普萘洛尔通过竞争性α-肾上腺素能受体拮抗作用选择性抑制α-肾上腺素能受体介导的血管收缩。