title: Nitric oxide-mediated relaxation to lactate of coronary circulation in the isolated perfused rat heart.
abstract: The objective of this study was to analyze the effects of lactate on coronary circulation. Rat hearts were perfused in a Langendorff preparation, and the coronary response to lactate (3-30 mM) was recorded after precontracting coronary vasculature with 11-dideoxy-1a,9a-epoxymethanoprostaglandin F2α (U46619), in the presence or the absence of the inhibitor of nitric oxide synthesis, N-omega-nitro-l-arginine methyl ester (l-NAME, 10 M), the blocker of Ca-dependent potassium channels, tetraethylammonium (TEA, 10 M), or the blocker of adenosine triphosphate-sensitive potassium channels, glybenclamide (10 M). The effects of lactate were also studied in isolated segments of rat coronary arteries that were precontracted with U46619, with or without endothelium. In perfused hearts, lactate induced concentration-dependent coronary vasodilatation and a reduction in myocardial contractility (left ventricular developed pressure and dP/dt) without altering the heart rate. Coronary vasodilatation in response to lactate was reduced by l-NAME but unaffected by TEA or glybenclamide. The effects of lactate on myocardial contractility were unchanged by l-NAME, TEA, or glybenclamide. In isolated coronary artery segments, lactate also produced relaxation, an effect attenuated by removing the endothelium. Together these findings suggest that lactate exerts coronary vasodilatory effects through the release of endothelial nitric oxide, independently of potassium channels. These findings may be relevant for the regulation of coronary circulation when lactate levels are elevated.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Montoya
authors.forename: Nuria
authors.initials: N
authors.lastname: Fernández
authors.forename: Luis
authors.initials: L
authors.lastname: Monge
authors.forename: Godofredo
authors.initials: G
authors.lastname: Diéguez
authors.forename: Angel Luis García
authors.initials: AL
authors.lastname: Villalón
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009569:Nitric Oxide; D019344:Lactic Acid; D019789:Tetraethylammonium; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester