Adrenomedullin causes coronary vasodilation in humans: effects of inhibition of nitric oxide synthesis.

Experimental studies have shown that adrenomedullin (AM) causes vasodilation, in part, mediated by endothelium-derived nitric oxide (NO). However, it remains to be clarified how NO is involved in AM-induced coronary vasoreactivity in humans. We examined whether NO contributes to the vasodilatory effects of adrenomedullin on human coronary arteries. In 10 patients with angiographically normal coronary arteries, adrenomedullin (low dose: I ng/kg/min; high dose: 10 ng/kg/min) was infused into the left coronary ostium before and after an infusion of N G -monomethyl-L-arginine (L-NMMA, 40 μmol/min for 5 min), an NO synthase inhibitor. Coronary diameter and coronary blood flow (CBF) were evaluated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to adrenomedullin were expressed as percent changes from baseline values. Adrenomedullin at a high dose dilated coronary arteries (3.7 ′ 0.5%, P < 0.001). Adrenomedullin increased the coronary blood flow at both doses (low: 55.7 ′ 13.9%, P < 0.01; high: 48.8 ′ 9.8%, P < 0.001). After the infusion of L-NMMA, adrenomedullin-induced coronary vasodilation and increase in coronary blood flow were attenuated. These findings suggest that adrenomedullin dilates human coronary arteries through an increase in NO production, at least in part.