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(Hypertension. 2001;38:1367.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Decreased Nitric Oxide Availability in Normotensive and Hypertensive Rats With Failing Hearts After Myocardial Infarction

Gabriele Wiemer; Gabi Itter; Tadeusz Malinski; Wolfgang Linz

From Aventis Pharma Deutschland, DG Cardiovascular Diseases, Frankfurt/Main, Germany (G.W., G.I., W.L.); and the Department of Chemistry and Biochemistry, Ohio University, Athens (T.M.).

Correspondence to Dr Wolfgang Linz, Aventis Deutschland GmbH, DG Cardiovascular Diseases (H813), D-65926 Frankfurt/Main Germany. E-mail wolfgang.linz{at}aventis.com

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.

Key Words: heart failure • endothelium • nitric oxide • rats, spontaneously hypertensive • rats, WKY

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