Myocardial contractile effects of nitric oxide.
Recent experimental and clinical research solved some of the controversies surrounding the myocardial contractile effects of NO. These controversies were: (1) does NO exert a contractile effect at baseline? (2) is NO a positive or a negative inotrope? (3) Are the contractile effects of NO similar when NO is derived from NO-donors or from the different isoforms of NO synthases (NOS)? (4) Does NO exert the same effects in hypertrophied, failing or ischemic myocardium? Transgenic mice with cardioselective overexpression of NOS revealed NO to produce a small reduction in basal developed LV pressure and a LV relaxation-hastening effect mainly through myofilamentary desensitization. Similar findings had previously been reported during intracoronary infusions of NO-donors in isolated rodent hearts and in humans. The LV relaxation hastening effect was accompanied by increased diastolic LV distensibility, which augmented LV preload reserve especially in heart failure patients. This beneficial effect on diastolic LV function always overrode the small NO-induced attenuation in LV developed pressure in terms of overall LV performance. In most experimental and clinical conditions, contractile effects of NO were similar when NO was derived from NO-donors or produced by the different isoforms of NOS. Because expression of inducible NOS (NOS2) is frequently accompanied by elevated oxidative stress, NO produced by NOS2 can lead to peroxynitrite-induced contractile impairment as observed in ischemic or septic myocardium. Finally, shifts in isoforms or in concentrations of myofilaments can affect NO-mediated myofilamentary desensitization and alter the myocardial contractile effects of NO in hypertrophied or failing myocardium.
Paulus
Walter J
WJ
Cardiovascular Center, OLV Ziekenhuis, Aalst, Belgium. walter.paulus@pi.be
Bronzwaer
Jean G F
JG
D000818:Animals; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D013599:Systole; D016277:Ventricular Function, Left / Q000502:physiology*
D009569:Nitric Oxide