title: Inducible nitric oxide synthase inhibits oxygen consumption in collateral-dependent myocardium.
abstract: Following coronary artery occlusion growth of collateral vessels can provide an effective blood supply to the dependent myocardium. The ischemia, which results in growth of collateral vessels, recruits an inflammatory response with expression of cytokines and growth factors, upregulation of endothelial nitric oxide (NO) synthase (eNOS) in vascular endothelial cells, and expression of inducible nitric oxide synthase (iNOS) in both vessels and cardiac myocytes. Because NO is a potent collateral vessel dilator, this study examined whether NO derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in the collateral region. Nonselective NOS inhibition with N(G)-nitro-l-arginine (LNA) caused vasoconstriction with a significant decrease in MBF to the collateral region during exercise. In contrast, the highly selective iNOS inhibitor 1400W caused a 21 ± 5% increase of MBF in the collateral region. This increase in MBF following selective iNOS blockade was proportionate to an increase in myocardial O2 consumption (MVo2). The results suggest that NO produced by iNOS inhibits MVo2 in the collateralized region, so that the increase in MBF following iNOS blockade was the result of metabolic vasodilation secondary to an increase in MVo2. Thus the coordinated expression of iNOS to restrain MVo2 and eNOS to maintain collateral vasodilation act to optimize the O2 supply-demand relationship and protect the collateralized myocardium from ischemia.
authors: Departments of Medicine and Integrative Biology/Physiology, University of Minnesota Medical School, Minneapolis, Minnesota; and.
authors: Yingjie
authors: Y
authors: Chen
authors: Ping
authors: P
authors: Zhang
authors: Jingxin
authors: J
authors: Li
authors: Xin
authors: X
authors: Xu
authors: Robert J
authors: RJ
authors: Bache
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000378:metabolism / Q000502:physiology; D004285:Dogs; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D014661:Vasoconstriction
chemical_list: D052247:Nitric Oxide Synthase Type II; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester
keywords: collateral vessel; coronary artery