Dose response studies with vasodilator antihypertensive drugs.

Vasodilators are highly efficacious in hypertension and the ideal one(s) have not yet been developed. Key information is obtained from initial studies of the effects of sequentially larger single oral doses. Blood pressure and heart rate responses measured in the recumbent and standing positions can be analyzed in terms of onset, dose response and offset of effect. These data, which can be modeled similarly to plasma concentration data, will determine the optimal dosing interval. The adequacy of blood pressure control should be confirmed by multiple dose administration. Orthostatic effect and intensity of compensatory responses can be evaluated by hemodynamic and neuroendocrine studies, the latter to include plasma catecholamines and plasma renin activity. Baroreflex sensitivity, as a determinant of autonomic response to vasodepression, appears to modify the response to intravenous nitroprusside, in part by increased sympathetic tone. The influence of baseline arterial pressure on the response to vasodilators may be partially determined by its inverse relationship to baroreflex sensitivity.