title: Decreased nitric oxide availability in normotensive and hypertensive rats with failing hearts after myocardial infarction.
abstract: Endothelial NO synthase, being deficient in arginine and/or tetrahydrobiopterin, produces in addition to NO a significant concentration of superoxide (O2)(-)). We investigated whether such an imbalance between O2(-) and NO production is present in dysfunctional aortas of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with failing hearts after myocardial infarction. Heart failure was induced by permanent occlusion of the left coronary artery, resulting in a large infarction of the free left ventricular wall. Eight weeks after myocardial infarction, when WKY and SHR had compensated heart failure and congestive heart failure, respectively, calcium ionophore-induced NO release (assessed by a NO-sensitive microsensor) from aortic endothelial cells was significantly reduced from 478+/-48 to 216+/-16 nmol/L and 693+/-131 to 257+/-53 nmol/L in WKY and SHR, respectively. Concomitantly, significant increases in calcium ionophore-stimulated O2(-) production (assessed by an electrochemical sensor) could be observed in aortic endothelial cells from infarcted WKY rats (22+/-3.2 versus sham, 10.1+/-1.2 nmol/L) and SHR (102+/-8 versus sham, 67+/-5 nmol/L). A dramatic increase in endothelial peroxynitrite concentration (chemiluminescence method) from 35+/-4 to 90+/-3 nmol/L for WKY and from 60+/-5 to 170+/-10 nmol/L for SHR also was detected. Thus, the markedly decreased NO availability probably caused by impaired endothelial NO synthase activity with enhanced O2(-) and peroxynitrite production appears to be attributable to endothelial dysfunction in normotensive rats with chronic heart failure and especially in hypertensive rats with severe congestive heart failure.
authors.affiliation: Aventis Pharma Deutschland, DG Cardiovascular Diseases, Frankfurt/Main, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wiemer
authors.forename: G
authors.initials: G
authors.lastname: Itter
authors.forename: T
authors.initials: T
authors.lastname: Malinski
authors.forename: W
authors.initials: W
authors.lastname: Linz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase