Beneficial effects of a nitric oxide donor on recovery of contractile function following brief hypoxia in isolated rat heart.

Brief myocardial hypoxia causes both systolic and diastolic dysfunction, the latter often persisting during re-oxygenation. The underlying mechanisms may involve cytosolic Ca2+ overload as well as altered myofilament properties. Recent studies show that nitric oxide enhances myocardial relaxation via a cGMP-induced reduction in myofilament response to Ca2+. We studied the effects of pretreatment with a nitric oxide donor, sodium nitroprusside (0.1-1 microM) on the response to 5 min hypoxia in isovolumic rat hearts perfused at constant coronary flow. Left ventricular relaxation was assessed by an exponential time constant of pressure fall. Sodium nitroprusside reduced the depression of peak left ventricular pressure and peak dP/dt during hypoxia, and improved left ventricular relaxation both during hypoxia and re-oxygenation. Similar results were observed with a Ca2+ antagonist, nicardipine (10 nM). However, adenosine (400 nM), which reduced coronary perfusion pressure to a similar extent as the other two drugs, failed to improve left ventricular function. Addition of sodium nitroprusside or nicardipine at re-oxygenation did not improve relaxation, but instead impaired recovery of peak left ventricular pressure. These results suggest that exogenous nitric oxide improves LV contractile function, in particular relaxation, during brief hypoxia-re-oxygenation independent of changes in coronary flow or coronary perfusion pressure. Its failure to be protective if administered only during re-oxygenation suggests that its action does not involve an anti-oxidant effect.