I1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives.

Moxonidine is an I1-imidazoline receptor agonist that reduces blood pressure in hypertensives. Experimental data suggest that moxonidine inhibits central sympathetic activity. However, whether such a mechanism is involved in vivo in humans is still unclear. We investigated the effects of 0.4 mg moxonidine orally on muscle sympathetic nerve activity and heart rate in an open study in 8 healthy volunteers. Furthermore, we studied the effects of 0.4 mg moxonidine on muscle sympathetic nerve activity, heart rate, blood pressure, 24-hour blood pressure profile, and hormone plasma levels in 25 untreated hypertensives in a double-blind, placebo-controlled study. Moxonidine decreased muscle sympathetic nerve activity in both healthy volunteers (P<0.05 versus baseline) and hypertensives (P<0.02 versus placebo). Plasma norepinephrine also decreased (P<0. 01), whereas plasma epinephrine and renin levels did not change (P=NS). Furthermore, moxonidine decreased systolic (P<0.0001) and diastolic (P<0.001) blood pressure. Heart rate decreased after moxonidine in healthy subjects (P<0.05); in hypertensives, heart rate decreased during the night hours (P<0.05) but not during daytime (P=NS). Plasma levels of LDL, HDL, and total cholesterol were not influenced by the drug (P=NS). Moxonidine decreases systolic and diastolic blood pressure by inhibiting central nervous sympathetic activity. This makes this new drug suitable for the treatment of human hypertension and possibly for other cardiovascular diseases with increased sympathetic nerve activity, ie, ischemic heart disease and heart failure.