Clonidine and prazosin effects in hypernoradrenergic vasodilator–treated and β‐blocker–treated patients

Our subjects were seven severely hypertensive patients with blood pressures (BPs) over 140/90 who were using minoxidil, propranolol, and diuretics. Clonidine followed by prazosin was added to their regimen on an outpatient basis to establish the dose‐response for BP and catecholamines. Plasma renin activity (PRA), body weight, and renal function were measured. Clonidine was given in doses of 0.2, 0.4, 0.6, and 0.8 mg/day. Supine and standing systolic BP decreased at all dose levels of clonidine (P < 0.01, P < 0.05). Diastolic BP decreased in the standing position with doses of 0.4, 0.6, and 0.8 mg (P < 0.01, P < 0.05). Subjects were hypernoradrenergic initially with plasma norepinephrine (PNE) 895 ± 122 pg/ml. PNE was suppressed by 0.2 to 0.8 mg clonidine (P < 0.01) with near maximal suppression at 0.4 mg daily. Systolic BP correlated with PNE (r = 0.59, P < 0.001). Supine and standing PRA decreased after 0.2 mg clonidine (P < 0.05) but not after higher doses. Our findings suggest the antihypertensive action of clonidine is related to PNE suppression but not to that of PRA. Plasma epinephrine (PE), body weight, and renal function did not change. Prazosin was given after clonidine to the same patients in a dose range of 3 to 40 mg/day. With doses of 6 to 40 mg, systolic and diastolic and supine and standing BP fell (P < 0.001, P < 0.01). PNE remained elevated throughout all dose levels and did not correlate with BP. Weight rose with prazosin (P < 0.02) but PE, PRA, and renal function did not change. Hence, clonidine and prazosin induced additional lowering of BP but had different effects on PNE and weight. Clinical Pharmacology and Therapeutics (1981) 30 , 297–302; doi: 10.1038/clpt.1981.163