Cardiomyocytes as effectors of nitric oxide signalling

Area of Science:

• Cardiovascular Physiology
• Molecular Cardiology
• Nitric Oxide Signaling

Background:

• Constitutive nitric oxide (NO) production in the heart impacts myocardial function.
• Previous research faced controversy due to non-selective inhibitors and NO donor studies.
• Recent advancements utilize isoform-selective inhibitors and genetic models for clarity.

Purpose of the Study:

• To review the current understanding of NO's role in myocardial contractile function.
• To highlight recent findings on the autocrine functions of nNOS-derived NO within cardiomyocytes.
• To discuss the influence of NOS isoforms on cardiac function, including relaxation, inotropy, and oxygen consumption.

Main Methods:

• Review of recent studies employing NOS-selective inhibitors.
• Analysis of data from genetically modified animal models.
• Examination of findings on eNOS and nNOS expression and localization within cardiomyocytes.

Main Results:

• Endothelial NO synthase (eNOS) in coronary endothelium affects cardiomyocyte relaxation and oxygen consumption via paracrine signaling.
• Both eNOS and neuronal NO synthase (nNOS) are constitutively expressed within cardiomyocytes at distinct subcellular locations.
• Evidence suggests nNOS autocrine signaling modulates basal inotropy, relaxation, and beta-adrenergic responsiveness.
• Myocardial eNOS may mediate inotropic responses to sustained stretch.

Conclusions:

• NO derived from distinct NOS isoforms within cardiomyocytes plays crucial autocrine roles in cardiac function.
• nNOS-derived NO appears to regulate basal contractility and responsiveness.
• eNOS in the heart may influence contractility under specific conditions like stretch.
• Altered NOS expression and activity in diseased hearts significantly impact NO signaling and cardiac function.