Attenuation by ACE inhibitor drugs of α-adrenoceptor sensitivity in human vessels: possible differences related to drug lipophilicity

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 α-adrenoceptor sensitivity was evaluated using the dorsal hand vein compliance technique. The dose–response curves of vasoconstriction to phenylephrine and prostaglandin F_2α 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 (E D ₅₀; 189.3 (57.6  ng  min⁻¹ ) of phenylephrine. Following quinapril administration, E D ₅₀ increased to 481.1 (101.8  ng  min⁻¹ compared with 266.8 (55.8  ng  min⁻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 PGF_2α .
Conclusions ACE inhibition attenuates α-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 α-adrenoceptor sensitivity of the vessels.