Isoproterenol-induced heart failure in the rat is associated with nitric oxide-dependent functional alterations of cardiac function.
OBJECTIVE
The role of nitric oxide (NO) in heart failure (HF) is complex and remains controversial. We tested the hypothesis that the role of NO in isolated atria and cardiomyocytes is altered in isoproterenol-induced HF.


RESULTS
Rats received isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) or vehicle for 1 week. Haemodynamic parameters were obtained by left ventricular catheterization. Effects of NOS inhibition on isolated atria and on electrically paced left ventricular myocytes were determined. Additionally, expressions of nitric oxide synthases and their allosteric modulators hsp90, caveolin-1, and caveolin-3 proteins in the left ventricles were measured. ISO increased left ventricular mass by 33% and decreased indices of left ventricular systolic and diastolic function dp/dtmin and dp/dtmax (both P<0.05). Isolated atria from HF rats had a lower spontaneous beating rate (P<0.05). NOS inhibition by L-NAME increased basal frequency and attenuated the positive chronotropic effect of beta-adrenergic stimulation in the HF group (P<0.05). Ventricular myocytes from failing hearts had impaired cell shortening. L-NAME decreased contractility of control, but not failing myocytes. Left ventricular expressions of eNOS, hsp90, iNOS, but not nNOS or caveolins, were increased.


CONCLUSIONS
Despite the increased capacity for NO synthesis in isoproterenol-induced HF, NO does not sustain contractility of failing myocytes. NO may contribute to the decreased basal heart rate and it may accelerate beta-adrenergic stimulation of chronotropy.
Krenek
Peter
P
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32 Bratislava, Slovak Republic. krenek@fpharm.uniba.sk
Kmecova
Jana
J
Kucerova
Dana
D
Bajuszova
Zuzana
Z
Musil
Peter
P
Gazova
Andrea
A
Ochodnicky
Peter
P
Klimas
Jan
J
Kyselovic
Jan
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006325:Heart Atria / Q000503:physiopathology; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester