Carvalho Beatriz M R, Bassani Rosana A, Franchini Kleber G, Bassani José W M
Centro de Engenharia Biomédica, Universidade Estadual de Campinas, Caixa Postal 6040, 13084-971 Campinas, SP, Brazil.
Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1803-13. doi: 10.1152/ajpheart.01345.2005. Epub 2006 Apr 28.
Early cardiovascular changes evoked by pressure overload (PO) may reveal adaptive strategies that allow immediate survival to the increased hemodynamic load. In this study, systolic and diastolic Ca(2+) cycling was analyzed in left ventricular rat myocytes before (day 2, PO-2d group) and after (day 7, PO-7d group) development of hypertrophy subsequent to aortic constriction, as well as in myocytes from time-matched sham-operated rats (sham group). Ca(2+) transient amplitude was significantly augmented in the PO-2d group. In the PO-7d group, intracellular Ca(2+) concentration (Ca(2+)) was reduced during diastole, and mechanical twitch relaxation (but not Ca(2+) decline) was slowed. In PO groups, fractional sarcoplasmic reticulum (SR) Ca(2+) release at a twitch, SR Ca(2+) content, SR Ca(2+) loss during diastole, and SR-dependent integrated Ca(2+) flux during twitch relaxation were significantly greater than in sham-operated groups, whereas the relaxation-associated Ca(2+) flux carried by the Na(+)/Ca(2+) exchanger was not significantly changed. In the PO-7d group, mRNA levels of cardiac isoforms of SR Ca(2+)-ATPase (SERCA2a), phospholamban, calsequestrin, ryanodine receptor, and NCX were not significantly altered, but the SERCA2a-to-phospholamban ratio was increased 2.5-fold. Moreover, greater sensitivity to the inotropic effects of the beta-adrenoceptor agonist isoproterenol was observed in the PO-7d group. The results indicate enhanced Ca(2+) cycling between SR and cytosol early after PO imposition, even before hypertrophy development. Increase in SR Ca(2+) uptake may contribute to enhancement of excitation-contraction coupling (augmented SR Ca(2+) content and release) and protection against arrhythmogenesis due to buildup of Ca(2+) during diastole.
压力超负荷（PO）引发的早期心血管变化可能揭示了一些适应性策略，这些策略能使机体在增加的血流动力学负荷下即刻存活。在本研究中，分析了主动脉缩窄后左心室大鼠心肌细胞在肥大发生前（第2天，PO - 2d组）和发生后（第7天，PO - 7d组）的收缩期和舒张期Ca(2+)循环情况，以及来自时间匹配的假手术大鼠（假手术组）的心肌细胞。PO - 2d组的Ca(2+)瞬变幅度显著增加。在PO - 7d组中，舒张期细胞内Ca(2+)浓度（Ca(2+)）降低，机械性抽搐舒张（但不是Ca(2+)下降）减慢。在PO组中，单次抽搐时肌浆网（SR）Ca(2+)释放分数、SR Ca(2+)含量、舒张期SR Ca(2+)丢失以及抽搐舒张期间SR依赖性综合Ca(2+)通量均显著高于假手术组，而由Na(+)/Ca(2+)交换体介导的与舒张相关的Ca(2+)通量无显著变化。在PO - 7d组中，SR Ca(2+)-ATP酶（SERCA2a）、受磷蛋白、肌集钙蛋白、雷诺丁受体和钠钙交换体（NCX）的心脏同工型的mRNA水平无显著改变，但SERCA2a与受磷蛋白的比值增加了2.5倍。此外，在PO - 7d组中观察到对β - 肾上腺素能受体激动剂异丙肾上腺素的变力作用具有更高的敏感性。结果表明，在施加PO后早期，甚至在肥大发展之前，SR与细胞质之间的Ca(2+)循环增强。SR Ca(2+)摄取增加可能有助于增强兴奋 - 收缩偶联（增加SR Ca(2+)含量和释放）以及防止因舒张期Ca(2+)蓄积而导致的心律失常。
