Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart.
Nitric oxide (NO) produced in the heart by nitric oxide synthase (NOS) is a highly reactive signaling molecule and an important modulator of myocardial function. NOS catalyzes the conversion of L: -arginine to L: -citrulline and NO but under particular circumstances reactive oxygen species (ROS) can be formed instead of NO (uncoupling). In the heart, three NOS isoforms are present: neuronal NOS (nNOS, NOS1) and endothelial NOS (eNOS, NOS3) are constitutively present enzymes in distinct subcellular locations within cardiomyocytes, whereas inducible NOS (iNOS, NOS2) is absent in the healthy heart, but its expression is induced by pro-inflammatory mediators. In the tissue, NO has two main effects: (i) NO stimulates the activity of guanylate cyclase, leading to cGMP generation and activation of protein kinase G, and (ii) NO nitrosylates tyrosine and thiol-groups of cysteine in proteins. Upon nitrosylation, proteins may change their properties. Changes in (i) NOS expression and activity, (ii) subcellular compartmentation of NOS activity, and (iii) the occurrence of uncoupling may lead to multiple NO-induced effects, some of which being particularly evident during myocardial overload as occurs during aortic constriction and myocardial infarction. Many of these NO-induced effects are considered to be cardioprotective but particularly if NOS becomes uncoupled, formation of ROS in combination with a low NO bioavailability predisposes for cardiac damage.
Umar
Soban
S
Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. S.umar@lumc.nl
van der Laarse
Arnoud
A
D006332:Cardiomegaly / Q000201:enzymology; D006333:Heart Failure / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology
D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III