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: 1 ng/kg/min; high dose: 10 ng/kg/min) was infused into the left coronary ostium before and after an infusion of N-monomethyl-L-arginine (L-NMMA, 40 micromol/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.
Ueda
Kentaro
K
Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Teragawa
Hiroki
H
Kimura
Masashi
M
Matsuda
Keiji
K
Higashi
Yukihito
Y
Yamagata
Togo
T
Oshima
Tetsuya
T
Yoshizumi
Masao
M
Chayama
Kazuaki
K
D053607:Adrenomedullin; D000368:Aged; D000787:Angina Pectoris / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase