Dose-response of clonidine on plasma catecholamines in the hypernoradrenergic state associated with vasodilator...

Six patients receiving minoxidil, propranolol, and diuretics had clonidine added in increasing dosage. Five patients received 0.2-0.8 mg/day clonidine and one patient 0.2-0.6 mg. Plasma catecholamines, renin activity, blood pressure, and serum creatinine were measured at each dose level. The patients had a hypernoradrenergic state prior to clonidine [mean +/- SE plasma norepinephrine (PNE), 924 +/- 141 pg/ml]. Administration of clonidine, 0.2-0.8 mg/day, lowered supine PNE (p less than 0.01, p less than 0.02), and clonidine, 0.4-0.8 mg/day, lowered standing PNE (p less than 0.01, p less than 0.02). Maximal suppression of PNE occurred with 0.4 mg/day. Systolic blood pressure correlated with supine PNE (r = 0.055, p less than 0.05) at 0.2-0.8 mg/day clonidine, and standing PNE correlated (r = 0.72, p less than 0.01) at 0.2-0.6 mg/day. Plasma epinephrine concentration, plasma renin activity (PRA), and serum creatinine did not show any significant change. PRA did not correlate with blood pressure changes. Plasma clonidine concentration correlated reciprocally with the change in PNE (r = -0.59, p less than 0.01). These findings indicate that clonidine can return elevated PNE to normal levels in the vasodilator beta-blocker-treated patient and thus remove this abnormality as a contributing factor to pathogenetic mechanisms.