Nitric oxide: A multifaceted modulator of cardiac contractility

The ubiquitous signaling molecule, nitric oxide (NO), has been shown to play a key role in many important cellular processes, including endothelium-dependent relaxation of blood vessels, chemical communication between peripheral nerves and smooth muscle, inhibition of platelet aggregation, immune responses and neurotransmission. In recent years a large body of information has appeared addressing the apparently multiple effects of NO and NO donors on myocardial contractility. These findings have often been seemingly contradictory. In this article we will review, and provide a synthesis, of the most recent findings on the wide range of actions of NO on myocardial contractility in an attempt to discriminate the downstream effecters, and to establish whether the multiple contractile responses to NO may be attributed to the activation of distinct cGMP- dependent or independent mechanisms.