title: Roles of systemic nitric oxide metabolites for human coronary circulation.
abstract: Several previous studies have suggested decreased bioactivity of nitric oxide (NO) in coronary artery diseases using NO synthase inhibitors. Nitrite is delivered as bioactive NO in the forearm circulation. However, the role(s) of NO metabolites in the systemic and coronary circulation are still unknown. The aim of this study was to investigate the role(s) of systemic NO metabolites for human coronary circulation in patients with and without coronary spastic angina (CSA). Twenty-nine patients with chest symptoms were enrolled to perform the acetylcholine (Ach) provocative test. Blood was sampled from the aorta at baseline, and from the great cardiac vein at baseline and after Ach to measure plasma levels of nitrate and nitrite (NOx). The epicardial left anterior descending artery was examined by quantitative angiography. The patients were divided into the two groups according to the Ach provocative test. In the non-CSA group, the NOx uptake across the coronary circulation correlated with the endothelium-dependent vasoresponse to Ach (r = -0.61, p < 0.05) and NOx levels of the aorta also correlated (r = -0.72, p < 0.005), which suggested the compensatory increase of systemic NOx levels for impaired endothelial function. In the CSA group, the NOx uptake across the coronary circulation did not correlate with the vasoresponse to Ach (r = 0.29, p = 0.28). However, NOx levels of the aorta correlated with vasosensitivity to Ach (r = 0.61, p < 0.005). The higher systemic NOx levels correlated well with the vasodilator responsiveness to Ach. These results suggest that systemic NOx is delivered into the coronary circulation as bioactive NO to preserve endothelial function in the non-CSA patients, and to attenuate Ach-induced vasoconstriction in the CSA patients. There is a possibility that systemic NOx plays a complementary role on impaired coronary vasoregulation.
authors.affiliation: The Cardiovascular Division, Ishinkai Yao General Hospital, Osaka 581-0036, Japan. kato-cl@ka2.so-net.ne.jp
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kato
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kijima
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Matsu-Ura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hashimura
authors.forename: Takenori
authors.initials: T
authors.lastname: Yasuda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ueda
authors.forename: Isao
authors.initials: I
authors.lastname: Mori
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000493:pharmacokinetics; D001011:Aorta / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D017023:Coronary Angiography / Q000379:methods; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D003920:Diabetes Mellitus / Q000175:diagnosis; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis; D007269:Injections, Intra-Arterial; D007564:Japan; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis; D009566:Nitrates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D009573:Nitrites / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018579:Patient Selection; D010361:Patients / Q000145:classification; D010601:Pharmacology, Clinical / Q000379:methods; D012907:Smoking
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D002784:Cholesterol; D000109:Acetylcholine