Hemodynamic effects of oxdralazine and hydralazine in hypertension

Oxdralazine, a pyridazine shown to induce prolonged arteriolar dilation in animals, was given orally in doses of 15 to 30 mg to 7 subjects with hypertension. Arterial pressure fell in 2 hr (average mean of 16 mm Hg), peaking in 3 to 4 hr, and was sustained for more than 6 hr. Cardiac output and heart rate rose in 2 hr (2.1 l/min and 17 bpm) and were elevated at 6 hr (3.1 l/min and 22 bpm). Pulmonary arterial pressure and pulmonary arteriolar resistance did not change. In 6 subjects receiving oxdralazine with hydralazine 50 to 75 mg at 1-wk intervals, hydralazine induced earlier, less sustained decreases in arterial pressure and systemic vascular resistance and less of a rise in heart rate than oxdralazine alone. Circulating norepinephrine levels (radioenzymatic method) 3 hr after oxdralazine rose from a mean of 159 to 294 pg/ml, a greater (p < 0.05) effect than after hydralazine. At the doses tested, oxdralazine is a potent systemic arteriolar dilator with longer-sustained action and more prominent reflex sympathetic stimulation than hydralazine.