title: Peroxynitrite irreversibly decreases diastolic and systolic function in cardiac muscle.
abstract: Much of the damaging action of nitric oxide in heart may be due to its diffusion-limited reaction with superoxide to form peroxynitrite. Direct infusion of peroxynitrite into isolated perfused hearts fails to model the effects of in situ formation because the bulk of peroxynitrite decomposes before reaching the myocytes. To examine the direct effects of peroxynitrite on the contractile apparatus of the heart, we exposed intact and skinned rat papillary muscles to a steady state concentration of 4-microM peroxynitrite for 5 min, followed by a 30-min recovery period to monitor irreversible effects. In intact muscles developed force fell immediately to 26% of initial force, recovering to 43% by 30 min. Resting tension increased by 600% immediately, and was still elevated 500% by 30 min. Nitrotyrosine immunochemistry showed that peroxynitrite can induce tyrosine nitration at low concentrations and is capable of penetrating 200-380 microm into the papillary muscle after a 5-min infusion. Decomposed peroxynitrite had no effect on either intact or skinned muscle developed force or resting tension. Our results show that peroxynitrite directly damages both developed force and resting tension of isolated heart muscle, which can be extrapolated to systolic and diastolic injury in intact hearts.
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Digerness
authors.forename: K D
authors.initials: KD
authors.lastname: Harris
authors.forename: J W
authors.initials: JW
authors.lastname: Kirklin
authors.forename: F
authors.initials: F
authors.lastname: Urthaler
authors.forename: L
authors.initials: L
authors.lastname: Viera
authors.forename: J S
authors.initials: JS
authors.lastname: Beckman
authors.forename: V
authors.initials: V
authors.lastname: Darley-Usmar
mesh_terms: D000818:Animals; D003971:Diastole / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009566:Nitrates / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D010210:Papillary Muscles / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013599:Systole / Q000187:drug effects*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D009566:Nitrates; D016877:Oxidants; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine