ANGIOTENSIN-CONVERTING ENZYME-INHIBITION ATTENUATES ARTERIAL CONSTRICTOR RESPONSES IN EXPERIMENTAL-HYPERTENSION

Angiotensin-converting enzyme inhibition has been shown to attenuate a rterial contractions, but the underlying mechanisms have not been clar ified in detail. Therefore, we investigated the effects of 10-week-lon g quinapril therapy (10 mg kg(-1) day(-1)) on responses of mesenteric arterial rings in vitro in spontaneously hypertensive rats (SHR) and n ormotensive Wistar-Kyoto rats. The hypertrophy of cardiac muscle and m esenteric arterial smooth muscle was effectively reduced in SHR by qui napril treatment. Maximal contractile force generation to 5-hydroxytry ptamine was reduced in endothelium-intact and -denuded rings of quinap ril-treated SHR when compared with untreated SHR. Contractile sensitiv ity of endothelium-intact rings to 5-hydroxytryptamine was also attenu ated in SHR by quinapril, whereas no differences were found between th e study groups in sensitivity of endothelium-denuded rings. Inhibition of NO synthesis by N-G-nitro-L-arginine methyl ester increased the se nsitivity and contractile force generation of endothelium-intact rings to 5-hydroxytryptamine more effectively in quinapril treated than in untreated SHR, whereas indomethacin had only minor effects on the resp onses in the study groups. Maximal responses and sensitivity to norepi nephrine were also reduced in SHR by quinapril and were more effective ly increased by N-G-nitro-L-arginine in quinapril-treated than in untr eated SHR. In addition, KCl-induced maximal contractions of endotheliu m-denuded rings were attenuated in quinapril-treated SHR. However, whe n the release of norepinephrine from vascular adrenergic nerve endings was eliminated by sympathectomy, no differences were found in maximal KCl-induced contractions between the study groups; this suggests that diminished contractions to KCl in quinapril-treated SHR resulted from reduced release of endogenous norepinephrine from vascular nerve endi ngs during depolarization. The inhibitory effects of the calcium chann el blocker nifedipine on arterial contractions in the Wistar-Kyoto rat groups and the quinapril-treated SHR were similar and were lower than in untreated SHR. In conclusion, the present findings suggest that ef fective reversal of cardiovascular hypertrophy, normalization of the f unction of voltage-dependent calcium channels, sympathoinhibitory acti on and enhanced endothelium-derived NO release can explain the attenua ted arterial constrictor responses that occur after the long-term inhi bition of angiotensin-converting enzyme.