血管紧张素转换酶抑制剂药物对人体血管α-肾上腺素能受体敏感性的减弱作用：与药物亲脂性相关的可能差异
Attenuation by ACE inhibitor drugs of alpha-adrenoceptor sensitivity in human vessels: possible differences related to drug lipophilicity.
作者信息
Kimura M, Umemura K, Kosuge K, Nishimoto M, Ohashi K, Nakashima M
机构信息
Department of Clinical Pharmacology, Hamamatsu University School of Medicine, Japan.
出版信息
Br J Clin Pharmacol. 1998 Dec;46(6):599-603. doi: 10.1046/j.1365-2125.1998.00834.x.
AIMS
We investigated the effect of angiotensin converting enzyme inhibitors (ACEIs) on postsynaptic adrenoceptor sensitivity and compared the effect of the lipophilic ACEI, quinapril, and that of hydrophilic agent, enalapril in human vessels.
METHODS
Alpha-adrenoceptor sensitivity was evaluated using the dorsal hand vein compliance technique. The dose-response curves of vasoconstriction to phenylephrine and prostaglandin F2alpha were obtained in healthy male volunteers.
RESULTS
The ACEIs shifted the dose-response curve of phenylephrine to the right and raised the median effective dose (ED50; 189.3 (57.6 ng min(-1)) of phenylephrine. Following quinapril administration, ED50 increased to 481.1 (101.8 ngmin(-1) compared with 266.8 (55.8 ngmin(-1) after enalapril (95% CI for differences; 31.1-397.5 ng min(-1)). Quinapril administration had no effect on the dose-response curve of PGF2alpha.
CONCLUSIONS
ACE inhibition attenuates alpha-adrenoceptor sensitivity in human vessels. The effect of quinapril, a lipophilic ACEI, was greater than that of enalapril, a hydrophilic ACEI. Lipophilic ACEIs may be more potent in vasodilating effect than hydrophilic ACEIs. Angiotensin II concentration in tissue rather than that in plasma may contribute to the alpha-adrenoceptor sensitivity of the vessels.
目的
我们研究了血管紧张素转换酶抑制剂（ACEI）对突触后肾上腺素能受体敏感性的影响，并比较了亲脂性ACEI喹那普利和亲水性药物依那普利对人体血管的作用。
方法
采用手背静脉顺应性技术评估α-肾上腺素能受体敏感性。在健康男性志愿者中获得去氧肾上腺素和前列腺素F2α血管收缩的剂量-反应曲线。
结果
ACEI使去氧肾上腺素的剂量-反应曲线右移，并提高了去氧肾上腺素的半数有效剂量（ED50；189.3（57.6 ng·min⁻¹））。服用喹那普利后，ED50增加至481.1（101.8 ng·min⁻¹），而依那普利后为266.8（55.8 ng·min⁻¹）（差异的95%置信区间；31.1 - 397.5 ng·min⁻¹）。喹那普利对PGF2α 的剂量-反应曲线无影响。
结论
ACE抑制可减弱人体血管中α-肾上腺素能受体的敏感性。亲脂性ACEI喹那普利的作用大于亲水性ACEI依那普利。亲脂性ACEI在血管舒张作用方面可能比亲水性ACEI更有效。组织而非血浆中的血管紧张素II浓度可能有助于血管的α-肾上腺素能受体敏感性。
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