Over the past 5 years there has been an explosion of new information on the physiological and pathophysiological roles of NO within the heart as in other organ systems. In this review, we focus primarily on the regulation of cardiac contractile function by NO. We do not cite many relevant earlier articles (eg, articles on the regulation of cardiac contractility by cyclic nucleotides) that can be accessed directly from references in the manuscripts that are cited, and we ask the forbearance of colleagues whose work has not been cited because of space constraints.

We begin with a brief description of the biochemistry of NO and of each of the three NOS isoforms that have been characterized to date. This is followed by a more detailed overview of the physiological roles of iNOS (or NOS2) and eNOS (or NOS3) in cardiac muscle. We end with a brief review of the effects of pharmacological donors of NO on ICa-L and of possible physiological actions of NO and related congeners that are not thought to be mediated via activation of guanylyl cyclase.