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.
D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D004431:Ear, External / Q000098:blood supply; D005260:Female; D006830:Hydralazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D006830:Hydralazine; D011189:Potassium Chloride; D000242:Cyclic AMP; D006152:Cyclic GMP; C006153:budralazine