Comparative haemodynamic effects of clonidine and guanfacine

Dose-response relationships were established for the acute effects on arterial pressure and heart rate of the antihypertensive agents, clonidine and guanfacine, administered intravenously or intramuscularly to anaesthetized rats. The intramuscular route appeared to be preferable to the intravenous, for the direct pressor potency of each drug was thereby greatly reduced in relation to the hypotensive efficacy. The potency of clonidine was 10-20 times that of guanfacine, but the same maximal fall in blood pressure was obtained with either agent administered by either route. Both agents caused a marked, dose-related suppression of plasma renin activity. When either clonidine or guanfacine was administered twice daily for 3 weeks and then discontinued, a phase of blood pressure overshoot with tachycardia commenced within 24 hr of the last injection. These withdrawal effects were more evident in guanfacine-treated rats than in clonidine-treated rats.