Tenner T E
Eur J Pharmacol. 1983 Aug 19;92(1-2):91-7. doi: 10.1016/0014-2999(83)90112-7.
The purpose of the present study was to determine if propranolol withdrawal supersensitivity could be demonstrated under in vitro conditions. Rats pretreated for 14 days with propranolol were studied 24, 48, 72 and 96 h after propranolol withdrawal. Right atria, right ventricle strips and thoracic aortic strips were isolated for study under in vitro conditions. Dose-response curves and geometric mean ED50 values revealed the presence of supersensitivity to the chronotropic and inotropic effects of isoproterenol in vitro at 72 and 96 h after withdrawal. No change in sensitivity was found 24 or 48 h after propranolol cessation. In like manner, supersensitivity to the vasorelaxant action of isoproterenol was demonstrated in aortic strips precontracted with angiotensin II at 72 and 96 h after propranolol withdrawal. In contrast, subsensitivity to the contractile actions of methoxamine was observed 48 h after withdrawal. These data indicate that chronic propranolol pretreatment and withdrawal results in the unmasking of supersensitivity to both beta 1 and beta 2 adrenoceptor stimulation. There would also appear to be a compensatory change in alpha-adrenoceptor-induced responses in rat aorta following propranolol withdrawal.
本研究的目的是确定在体外条件下是否能证明普萘洛尔撤药超敏反应。对用普萘洛尔预处理14天的大鼠，在撤药后24、48、72和96小时进行研究。分离右心房、右心室条带和胸主动脉条带，在体外条件下进行研究。剂量-反应曲线和几何平均ED50值显示，在撤药后72和96小时，体外对异丙肾上腺素的变时和变力作用存在超敏反应。在普萘洛尔停药后24或48小时未发现敏感性变化。同样，在普萘洛尔撤药后72和96小时，在与血管紧张素II预收缩的主动脉条带中，对异丙肾上腺素的血管舒张作用表现出超敏反应。相反，在撤药后48小时观察到对甲氧明收缩作用的低敏反应。这些数据表明，慢性普萘洛尔预处理和撤药导致对β1和β2肾上腺素能受体刺激的超敏反应显现出来。在普萘洛尔撤药后，大鼠主动脉中α-肾上腺素能受体诱导的反应似乎也有代偿性变化。
