HEMODYNAMIC AND ENDOCRINE RESPONSES TO GUANFACINE IN NORMOTENSIVE VOLUNTEERS AND HYPERTENSIVE PATIENTS

The centrally acting alphamimetic antihypertensive drug, guanfacine, was studied in normotensive volunteers and patients with essential and renal hypertension. After acute (0.02 mg/kg, intravenously) and short-term (mean dose: 6.7 mg/kg orally for 4 weeks) administration of guanfacine, systolic, diastolic and mean blood pressure (BPs), heart rate, cardiac output and right atrial pressure were measured by standard techniques. Cardiac index, stroke volume and total peripheral vascular resistance were calculated. After medium-term therapy (mean dose: 6 mg/kg orally for 12 weeks), antihypertensive efficacy, as well as plasma renin activity and catecholamine levels, was determined. After intravenous administration, guanfacine lowered systolic, diastolic and mean arterial BPs after a brief and transient increase. Guanfacine exerted its antihypertensive action primarly by its effect on total peripheral resistance. Reflex tachycardia was not observed. Heart rate was reduced. Stroke volume increased and right atrial pressure decreased. These effects were maintained or enhanced during the 4 weeks of oral therapy that followed. In the 12-week study, significant reductions in systolic, diastolic and mean BPs were observed. With a constant dose of 3 mg/day for 1 week, BP decreased from 197/115/149 (systolic/diastolic/mean) to 166/97/126 mm Hg. After 4 weeks at varying doses, BP decreased to 157/91/118, and after 12 weeks, to 147/83/109. In the 12 patients treated for 4 weeks with 3 mg/day, a significant decrease from 192/111/145 to 151/87/114 mm Hg was observed, while in the 6 patients treated for 12 weeks with the 3 mg/day dose, the final readings showed a decrease of 50 mm Hg in systolic pressure, 30 mm Hg in diastolic pressure and 38.4 mm Hg in mean arterial pressure. Renin and catecholamine values decreased during therapy, but at no time during treatment did these decreases correlate with those of BP.