Role of inducible nitric oxide synthase in myocardial ischemia-reperfusion injury in sleep-deprived rats.

Abstract

REM sleep deprivation (SD) decreases tolerance of the rat heart to ischemia-reperfusion (IR) injury; the underlying mechanisms, however, are unknown. This study aimed at determining whether changes in iNOS, Bax, and Bcl-2 gene expression are involved in this detrimental effect. SD was induced by flowerpot technique for a period of 4days. This method is simple and able to induce sleep fragmentation which occurs as one of the sleep disorder symptoms in clinical conditions. The hearts of control and SD rats were perfused in Langendorff apparatus and subjected to 30min ischemia, followed by 90min reperfusion. The hemodynamic parameters (left ventricular developed pressure (LVDP), and ±dp/dt), NOx (nitrite+nitrate) level, infarct size, and mRNA expression of iNOS, Bax, and Bcl-2 were measured after IR. SD rats had lower recovery of post-ischemic LVDP (32.8±2.5 vs. 51.5±2.1mmHg; P<0.05), +dp/dt (1555±66 vs. 1119.5±87mmHg/s; P<0.05) and -dp/dt (1437±65 vs. 888±162mmHg/s; P<0.05). SD rats also had higher NOx levels (41.4±3.1 vs. 22.4±3.6μmol/L; P<0.05) and infarct size (64.3±2.3 vs. 38.3±1.6%; P<0.05) after IR, which along with LVDP, ±dp/dt restored to near normal status in the presence of aminoguanidine, a selective iNOS inhibitor. Following IR, expression of iNOS and Bax increased and Bcl-2 decreased (502, 372, and 54%, respectively) in SD rats; whereas in the presence of aminoguanidine, expression of iNOS and Bax significantly decreased and Bcl-2 increased (165, 168, and 19%, respectively). Higher expression of iNOS and subsequent increase in apoptosis in the hearts after IR may contribute to less tolerance to myocardial IR injury in SD rats.