Dept. of Cell Biology, Univ. of Calabria, 87030 Arcavacata di Rende, CS, Italy.
Am J Physiol Regul Integr Comp Physiol. 2012 Jun;302(11):R1271-81. doi: 10.1152/ajpregu.00616.2011. Epub 2012 Apr 4.
Evidence from both mammalian and nonmammalian vertebrates indicates that intracardiac nitric oxide (NO) facilitates myocardial relaxation, ventricular diastolic distensibility, and, consequently, the Frank-Starling response, i.e., the preload-induced increase of cardiac output. Since nitrite ion (NO(2)(-)), the major storage pool of bioactive NO, recently emerged as a cardioprotective endogenous modulator, we explored its influence on the Frank-Starling response in eel, frog, and rat hearts, used as paradigms of fish, amphibians, and mammals, respectively. We demonstrated that, like NO, exogenous nitrite improves the Frank-Starling response in all species, as indicated by an increase of stroke volume and stroke work (eel and frog) and of left ventricular (LV) pressure and LVdP/dt max (rat), used as indexes of inotropism. Unlike in frog and rat, in eel, the positive influence of nitrite appeared to be dependent on NO synthase inhibition. In all species, the effect was sensitive to NO scavengers, independent on nitroxyl anion, and mediated by a cGMP/PKG-dependent pathway. Moreover, the nitrite treatment increased S-nitrosylation of lower-molecular-weight proteins in cytosolic and membrane fractions. These results suggest that nitrite acts as a physiological source of NO, modulating through different species-specific mechanisms, the stretch-induced intrinsic regulation of the vertebrate heart.
来自哺乳动物和非哺乳动物脊椎动物的证据表明，心内一氧化氮（NO）有助于心肌松弛、心室舒张延展性，从而促进Frank-Starling 反应，即前负荷诱导的心输出量增加。由于亚硝酸盐离子（NO2(-)）是生物活性 NO 的主要储存库，最近作为一种心脏保护性内源性调节剂出现，我们探讨了它对鳗鱼、青蛙和大鼠心脏Frank-Starling 反应的影响，分别用作鱼类、两栖类和哺乳动物的模型。我们证明，与 NO 一样，外源性亚硝酸盐可改善所有物种的 Frank-Starling 反应，这表现为心搏量和每搏功（鳗鱼和青蛙）以及左心室（LV）压力和 LVdP/dt max（大鼠）的增加，作为变力性的指标。与青蛙和大鼠不同，在鳗鱼中，亚硝酸盐的积极影响似乎依赖于一氧化氮合酶抑制。在所有物种中，该作用对 NO 清除剂敏感，与硝普盐阴离子无关，并且通过 cGMP/PKG 依赖性途径介导。此外，亚硝酸盐处理增加了细胞质和膜部分中小分子量蛋白质的 S-亚硝基化。这些结果表明，亚硝酸盐作为 NO 的生理来源，通过不同的种特异性机制调节脊椎动物心脏的伸展诱导的固有调节。
