Characterization of the vasodilator action of antihypertensive drug budralazine.

Intravenous injection of 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]phthalazine (budralazine) to anesthetized dogs resulted in an increase in cardiac output and regional blood flow in various vascular beds, and a fall in mean blood pressure with a decreased total and regional vascular resistance. Budralazine produced a dose-related increase in femoral blood flow in anesthetized dogs when injected into the femoral artery. The vasodilator drug relaxed either KCl(K+)- or noradrenaline (NA)-induced contractions of isolated rabbit aorta in a concentration-dependent manner. In the K+-depolarized aorta, it also produced a concentration-related inhibition of contractile response to cumulative addition of Ca2+. Intra-arterial injection of budralazine dilated dose-dependently the isolated perfused vascular bed of rabbit ear constricted by either K+ or NA. Budralazine, at effective antihypertensive oral dose, was without significant effect on cyclic nucleotide levels in the aorta of spontaneously hypertensive rats (SHR). These results indicate that budralazine, like hydralazine, produces vasodilation through a direct effect on vascular smooth muscle which may result at least in part from its inhibitory effect on vascular Ca2+ fluxes.