Lack of inotropic effect of nitric oxide on the rat myocardium

1. Nitric oxide (NO) is an important mediator of contractile function in the heart. However, isolated papillary muscle preparations appear to lack NO responsiveness in certain animal species. Although cat, guinea-pig and ferret models have been NO responsive, there have been mixed results in the rat papillary muscle. In null form, we tested three separate hypotheses in rat papillary muscle, specifically that the NO donor sodium nitroprusside (SNP) would not affect the contractility of: (i) the isolated papillary muscle; (ii) papillary muscle prestimulated with the beta-adrenoceptor agonist isoprenaline; and (iii) papillary muscle subjected to 15 min anoxia followed by 45 min reoxygenation. 2. Male Sprague-Dawley rats were used. The left ventricular papillary muscle was mounted and maintained at 30 degrees C and was stimulated at 10 b.p.m. Each experiment was performed in parallel with a control papillary muscle from the same animal. Papillary muscles were exposed to increasing concentrations of SNP (10(-9) to 10(-5) mol/L) either alone or following pretreatment with 10(-7) mol/L isoprenaline. Anoxia/reoxygenation was simulated by 15 min anoxia followed by 60 min reoxygenation in the presence or absence of 10(-7) mol/L SNP. 3. Both isometric and isotonic parameters were assessed. As expected, isoprenaline had a significant positive inotropic response. Similarly, contractility was impaired during anoxia and partially recovered during reoxygenation. Nitric oxide did not alter either isotonic or isometric parameters in the three experimental protocols. 4. The rat isolated papillary muscle has no measurable response to exogenous NO. The inotropic effects of beta-adrenoceptor stimulation and anoxia/reoxygenation are NO independent.