title: Reduced NO-dependent arteriolar dilation during the development of cardiomyopathy.
abstract: Our previous studies have suggested that there is reduced nitric oxide (NO) production in canine coronary blood vessels after the development of pacing-induced heart failure. The goal of these studies was to determine whether flow-induced NO-mediated dilation is altered in coronary arterioles during the development of heart failure. Subepicardial coronary arterioles (basal diameter 80 microm) were isolated from normal canine hearts, from hearts with dysfunction but no heart failure, and from hearts with severe cardiac decompensation. Arterioles were perfused at increasing flow or administered agonists with no flow in vitro. In arterioles from normal hearts, flow increased arteriolar diameter, with one-half of the response being NO dependent and one-half prostaglandin dependent. Shear stress-induced dilation was eliminated by removing the endothelium. Arterioles from normal hearts and hearts with dysfunction but no failure responded to increasing shear stress with dilation that reached a maximum at a shear stress of 20 dyn/cm(2). In contrast, arterioles from failing hearts showed a reduced dilation, reaching only 55% of the dilation seen in vessels of normal hearts at a shear stress of 100 dyn/cm(2). This remaining dilation was eliminated by indomethacin, suggesting that the NO-dependent component was absent in coronary microvessels after the development of heart failure. Similarly, agonist-induced NO-dependent coronary arteriolar dilation was markedly attenuated after the development of heart failure. After the development of severe dilated cardiomyopathy and heart failure, the NO-dependent component of both shear stress- and agonist-induced arteriolar dilation is reduced or entirely absent.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: A
authors.initials: A
authors.lastname: Huang
authors.forename: G
authors.initials: G
authors.lastname: Zhao
authors.forename: R
authors.initials: R
authors.lastname: Bernstein
authors.forename: P
authors.initials: P
authors.lastname: Forfia
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: A
authors.initials: A
authors.lastname: Koller
authors.forename: G
authors.initials: G
authors.lastname: Kaley
authors.forename: T H
authors.initials: TH
authors.lastname: Hintze
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology*; D002303:Cardiac Output, Low / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D009202:Cardiomyopathies / Q000503:physiopathology*; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D006439:Hemodynamics; D009569:Nitric Oxide / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide