Studies on the direct vasodilator effect of hydralazine in the isolated rabbit renal artery

In contrast to other large arteries commonly used in organ bath studies, the rabbit renal artery is highly sensitive to the vasodilator action of hydralazine. Helical strips contracted by 10(-7) M norepinephrine started to relax at a threshold concentration of 3.9 x 10(-8) M hydralazine (IC10). The IC50 was 1.4 x 10(-7) M, and at 3 x 10(-6) M hydralazine, the preparations had relaxed almost completely. The development of relaxation was slow, lasting up to 1 hr. Dose-response curves to norepinephrine in the presence of hydralazine were shifted to the right in parallel fashion at an only slight reduction of the maximum response. Contractions of rabbit renal artery strips induced by 45 mM, KCl, or by 10(-7) M norepinephrine superimposed on the KCl-induced tone, were almost unresponsive to hydralazine. Similarly, prolonged incubation of the arterial strips with 10(-5) M ouabain abolished the response to hydralazine probably as a result of a ouabain-induced depolarization. Neither indomethacin, an inhibitor of tissue prostaglandin synthesis, nor sulpiride, an antagonist to dopamine, interfered significantly with the vasodilator action of hydralazine. This suggests that the relaxant effect of hydralazine is not mediated by locally formed prostaglandins and that it is not dopaminergic in nature. The present findings indicate that hydralazine is a potent direct vasodilator with a predominant action on pharmacomechanical coupling but little effect on electromechanical coupling.