Nitric oxide inhibits isoprenaline-induced positive inotropic effects in normal, but not in hypertrophied rat heart.
Evidence has accumulated that, in the rat heart, nitric oxide (NO) inhibits beta-adrenoceptor-mediated positive inotropic effects. The aim of this study was to investigate whether this effect of NO may be altered in cardiac hypertrophy. For this purpose we studied the effects of the NO-donor SNAP (S-nitroso-N-acetyl-D,L-penicillamine) on isoprenaline-induced positive inotropic effects in left ventricular strips from three models of cardiac hypertrophy: a) 12-16 weeks old male spontaneously hypertensive rats (SHR) vs. age-matched normotensive Wistar-Kyoto (WKY) rats, b) six weeks old male Wistar WKY-rats sub-totally nephrectomized (SNX) 7 weeks after SNX vs. sham-operated rats (SOP) and c) four weeks old male Wistar WKY-rats supra-renal aortic-banded (AOB, band diameter 1.0 mm) 8 weeks after AOB vs. SOP. In all three models of cardiac hypertrophy the heart weight/body weight ratio was significantly higher than in their respective controls. On isolated electrically driven ventricular strips isoprenaline (10(-10)-10(-5) M) caused concentration-dependent increases in force of contraction. Maximal increases (Emax) were similar in SHR vs. WKY-rats, but reduced in SNX- (2.9+/-0.29 vs. 5.1+/-0.34 mN, p<0.01) and AOB-rats (2.3+/-0.37 vs. 4.2+/-0.33 mN, p<0.01). In control rats (WKY and the respective SOP) the NO-donor SNAP (10(-5) M) caused a significant rightward-shift of the concentration-response curve for isoprenalinel; this rightward-shift could be inhibited by methylene blue (10(-5) M). In ventricular strips of SHR, SNX- and AOB-rats, however, 10(-5) M SNAP failed to significantly affect isoprenaline-induced positive inotropic effect. We conclude that in cardiac hypertrophy effects of NO are attenuated. Such an impairement of the NO-system could contribute to the development and/or maintenance of cardiac hypertrophy.
Kotchi Kotchi
E
E
Institute of Pharmacology and Toxicology, Martin-Luther-University of Halle-Wittenberg, Halle, Germany.
Weisselberg
T
T
Röhnert
P
P
Preiss
M
M
Heinroth-Hoffmann
I
I
Osten
B
B
Brodde
O E
OE
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D001012:Aorta, Abdominal; D006332:Cardiomegaly / Q000188:drug therapy / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000502:physiology; D008297:Male; D009392:Nephrectomy; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012016:Reference Values
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D010396:Penicillamine; D007545:Isoproterenol