Relevance of nitric oxide for myocardial remodeling.
Endogenous myocardial nitric oxide (NO) may modulate the transition from adaptive to maladaptive remodeling leading to heart failure. In rodent models of pressure overload or myocardial infarction, the three NO synthase (NOS) isoforms were shown to play a neutral, protective, or even adverse role in myocardial remodeling, depending on the quantity of NO produced, the location of each NOS and their regulators, the prevailing oxidant stress and resultant NO/oxidant balance, as well as NOS coupling/dimerization. Beside neuronal NOS and--in specific conditions--inducible NOS isoforms, endothelial NOS (eNOS) exerts cardioprotective effects on pressure-overload, ischemia/reperfusion, and myocardial infarction-induced myocardial remodeling, provided the enzyme remains in a coupled state. Besides its effects on excitation-contraction coupling in response to stretch, eNOS acts as an "endogenous beta-blocker" by restoring the sympathovagal balance, opposing excessive hypertrophy as well as promoting vasodilatation and neoangiogenesis, thereby contributing to tissue repair. As eNOS was also shown to mediate the beneficial effects of cardiovascular drugs commonly used in patients with heart failure, strategies to increase its expression and/or coupled catalytic activity in the myocardium offer new therapeutic avenues for the treatment of this disease.
Massion
Paul B
PB
Unit of Pharmacology and Therapeutics (FATH 5349), Department of Medicine, Université Catholique de Louvain, 53 Avenue Mounier, 1200 Brussels, Belgium.
Balligand
Jean-Luc
JL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III