Myocardial Nitric Oxide in Heart Failure

Over the past decade, evidence has emerged that nitric oxide (NO·) may play a role in the pathogenesis of myocardial failure. The effects of NO· in myocardial failure, as in other clinical situations, may be either beneficial or deleterious. NO· at relatively low levels appears to modulate the response of the myocardium to potentially deleterious stimuli, and thus in some situations may offset the progression of myocardial failure. On the other hand, at higher levels NO· has the ability to impair normal myocardial function and to exert direct toxic effects in the myocardium, as it can in other tissues. The effects of higher levels of NO· may be relevant to a variety of situations in which myocardial NO· is increased. These include conditions in which there is a clear inflammatory reaction such as sepsis, myocarditis, transplant rejection or acute infarction. There is now evidence that NO· production is also increased above physiologic levels in the myocardium of patients with chronic heart failure. These observations have led to the concern that with increasing levels, NO· may contribute to the pathogenesis of myocardial failure, and thus change from a friend to a foe.