Hemodynamic effects of cadralazine in hexamethonium treated and non-treated anesthetized dogs

Hemodynamic effects of the newly synthesized vasodilator cadralazine (ethyl(+/)-6-[ethyl(2-hydroxypropyl)amino]-3- pyridazinecarbazate) were compared with those of hydralazine and budralazine in hexamethonium treated and non-treated anesthetized dogs. In hexamethonium non-treated dogs, cadralazine (1 and 3 mg/kg i.v.) exerted a dose-dependent and sustained decrease in systolic and diastolic arterial blood pressure similar to that of budralazine (10 mg/kg i.v.) and the effect was slow in onset and long lasting until 5 h after administration compared with hydralazine (0.5 and 1 mg/kg i.v.). Total peripheral vascular resistance was decreased by these three drugs. The common carotid, femoral and renal arterial blood flow increased as a result of the decrease in vascular resistance, but the superior mesenteric arterial flow has not significantly changed. Blood flow increase in the renal artery was fast and that in the femoral artery was predominant. Treatment with hexamethonium decreased blood pressure, but cadralazine caused a further decrease within 60 min similarly to the decrease pattern of hydralazine. Common carotid and femoral arterial vascular resistance also decreased by hexamethonium treatment and a further decrease was observed by administration of cadralazine. Heart rate and cardiac output were immediately and significantly increased by cadralazine, but the increment in heart rate was diminished by the treatment with hexamethonium. Therefore the tachycardiac response is assumed to be caused by baroreceptor reflex and compensates the decrease in vascular resistance which results in moderation of manifestation of the early stage hypotensive effect of cadralazine.