Angiotensin-converting enzyme inhibition has been shown to attenuate arterial contractions, but the underlying mechanisms have not been clarified in detail. Therefore, we investigated the effects of 10-week-long quinapril therapy (10 mg kg-1 day-1) on responses of mesenteric arterial rings in vitro in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats. The hypertrophy of cardiac muscle and mesenteric arterial smooth muscle was effectively reduced in SHR by quinapril treatment. Maximal contractile force generation to 5-hydroxy-tryptamine was reduced in endothelium-intact and -denuded rings of quinapril-treated SHR when compared with untreated SHR. Contractile sensitivity of endothelium-intact rings to 5-hydroxytryptamine was also attenuated in SHR by quinapril, whereas no differences were found between the study groups in sensitivity of endothelium-denuded rings. Inhibition of NO synthesis by NG-nitro-L-arginine methyl ester increased the sensitivity 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 responses in the study groups. Maximal responses and sensitivity to norepinephrine were also reduced in SHR by quinapril and were more effectively increased by NG-nitro-L-arginine in quinapril-treated than in untreated SHR. In addition, KCI-induced maximal contractions of endothelium-denuded rings were attenuated in quinapril-treated SHR. However, when the release of norepinephrine from vascular adrenergic nerve endings was eliminated by sympathectomy, no differences were found in maximal KCI-induced contractions between the study groups; this suggests that diminished contractions to KCI in quinapril-treated SHR resulted from reduced release of endogenous norepinephrine from vascular nerve endings during depolarization. The inhibitory effects of the calcium channel 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 effective reversal of cardiovascular hypertrophy, normalization of the function of voltage-dependent calcium channels, sympathoinhibitory action and enhanced endothelium-derived NO release can explain the attenuated arterial constrictor responses that occur after the long-term inhibition of angiotensin-converting enzyme.