I-1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives

Moxonidine is an I-1-imidazoline receptor agonist that reduces blood pressu re in hypertensives. Experimental data suggest that moxonidine inhibits cen tral sympathetic activity. However, whether such a mechanism is involved in vivo in humans is still unclear. We investigated the effects of 0.4 mg mox onidine orally on muscle sympathetic nerve activity and heart rate in an op en study in 8 healthy volunteers. Furthermore, we studied the effects of 0. 4 mg moxonidine on muscle sympathetic nerve activity, heart rate, blood pre ssure, 24-hour blood pressure profile, and hormone plasma levels in 25 untr eated 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 nor epinephrine also decreased (P<0.01), whereas plasma epinephrine and renin l evels 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 decre ased 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 inhibi ting central nervous sympathetic activity. This makes this new drug suitabl e for the treatment of human hypertension and possibly for other cardiovasc ular diseases with increased sympathetic nerve activity, ie, ischemic heart disease and heart failure.