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.
RCT Entities:
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.
Authors: G S Francis; C Benedict; D E Johnstone; P C Kirlin; J Nicklas; C S Liang; S H Kubo; E Rudin-Toretsky; S Yusuf Journal: Circulation Date: 1990-11 Impact factor: 29.690
Authors: J N Cohn; T B Levine; M T Olivari; V Garberg; D Lura; G S Francis; A B Simon; T Rector Journal: N Engl J Med Date: 1984-09-27 Impact factor: 91.245