Kotchi Kotchi E, Weisselberg T, Röhnert P, Preiss M, Heinroth-Hoffmann I, Osten B, Brodde O E
Institute of Pharmacology and Toxicology, Martin-Luther-University of Halle-Wittenberg, Halle, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1998 May;357(5):579-83. doi: 10.1007/pl00005211.
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.
已有证据表明，在大鼠心脏中，一氧化氮（NO）可抑制β-肾上腺素能受体介导的正性肌力作用。本研究的目的是探讨在心肌肥厚时，NO的这种作用是否会发生改变。为此，我们研究了NO供体SNAP（S-亚硝基-N-乙酰-D，L-青霉胺）对三种心肌肥厚模型左心室条带中异丙肾上腺素诱导的正性肌力作用的影响：a）12 - 16周龄雄性自发性高血压大鼠（SHR）与年龄匹配的正常血压Wistar-Kyoto（WKY）大鼠；b）6周龄雄性Wistar WKY大鼠在肾次全切除（SNX）7周后与假手术大鼠（SOP）；c）4周龄雄性Wistar WKY大鼠在腹主动脉缩窄（AOB，缩窄环直径1.0 mm）8周后与SOP。在所有三种心肌肥厚模型中，心脏重量/体重比均显著高于各自的对照组。在离体电驱动的心室条带上，异丙肾上腺素（10^(-10) - 10^(-5) M）引起收缩力的浓度依赖性增加。SHR与WKY大鼠的最大增加量（Emax）相似，但在SNX大鼠（2.9±0.29对5.1±0.34 mN，p<0.01）和AOB大鼠（2.3±0.37对4.2±0.33 mN，p<0.01）中降低。在对照大鼠（WKY和各自的SOP）中，NO供体SNAP（10^(-5) M）导致异丙肾上腺素浓度-反应曲线显著右移；这种右移可被亚甲蓝（10^(-5) M）抑制。然而，在SHR、SNX和AOB大鼠的心室条带中，10^(-5) M的SNAP未能显著影响异丙肾上腺素诱导的正性肌力作用。我们得出结论，在心肌肥厚时，NO的作用减弱。NO系统的这种损害可能有助于心肌肥厚的发生和/或维持。
