Diazepam Attenuates Phenylephrine-Induced Contractions in Rat Aorta

In this in vitro study we examined the effects of diazepam on a phenylephrine-induced contraction in rat aorta and determined the associated cellular mechanism focusing on the endothelium-derived vasodilators. The concentration-response curves for phenylephrine and potassium chloride were generated in the presence or absence of diazepam. Phenylephrine concentration-response curves were generated from the endothelium-intact rings pretreated independently with NW-nitro-l-arginine methyl ester, PK 11195, tetraethylammonium, and indomethacin in the presence or absence of diazepam. Diazepam (7 × 10−7 M) attenuated the phenylephrine-induced contraction in the endothelium-intact rings, whereas a large dose (5 × 10−6 M) of diazepam attenuated the phenylephrine-induced contraction in the aortic rings with or without the endothelium. A pretreatment with the NW-nitro-l-arginine methyl ester completely abolished the diazepam (7 × 10−7 M)-induced attenuation of the phenylephrine concentration-response curve, as well as the diazepam (5 × 10−6 M)-induced attenuation of the maximal contractile response to phenylephrine. The NW-nitro-l-arginine methyl ester (10−4 M)-induced contraction was enhanced in the rings pretreated with diazepam (5 × 10−6 M). These results indicate that a supraclinical concentration of diazepam attenuates phenylephrine-induced contraction by increasing endothelial nitric oxide activity and directly affecting vascular smooth muscle.