Sustained inhibition of nitric oxide by NG-nitro-L-arginine improves myocardial function following ischemia/reperfusion in isolated perfused rat heart.
It has been postulated that nitric oxide (NO) can react with superoxide anion (.O2-) to generate hydroxyl (.OH) radical. If this is correct, inhibition of NO synthesis could attenuate .OH radical mediated ischemia/reperfusion injury. Therefore we studied the effects of NG-nitro-L-arginine (L-NNA), a competitive inhibitor of the NO synthase enzyme on ischemia/reperfusion injury injury in isolated perfused rat hearts. Three groups of rats (n = 12-15) were studied. Group I: Untreated ischemia/reperfusion control (37.5 min of global ischemia followed by 20 min reperfusion); Group II: ischemia/reperfusion with 25 microM NG-nitro-L-arginine; and Group III: ischemia/reperfusion in the presence of L-NNA and 2 mM L-arginine, the substrate for NO synthase. Coronary flow (in ml/min) and ventricular developed pressure, +dP/dt and -dP/dt were measured 5 min prior to ischemia and at the end of reperfusion. Baseline preischemic developed pressure was significantly lower in L-NNA perfused hearts than controls (76.8 +/- 5.9 v 97.6 +/- 2.9 mmHg, P < 0.05). However, the developed pressure following reperfusion was significantly greater in L-NNA perfused hearts (57.4 +/- 7.4 v 20.8 +/- 6.4 mmHg in control). This protective effect was reversed by the addition of L-arginine. Preischemic coronary flow was decreased significantly in the L-NNA group (6.4 +/- 0.5 ml/min) compared to controls (11.6 +/- 0.7 ml/min). The duration of sinus rhythm was significantly improved from 3.8 +/- 1.2 min in controls to 15.1 +/- 0.8 min in L-NNA perfused hearts. A corresponding significantly lower incidence of arrhythmias was observed (10.2 +/- 1.5 in ischemia/reperfusion group v 1.7 +/- 0.8 min with L-NNA).(ABSTRACT TRUNCATED AT 250 WORDS)
Naseem
S A
SA
Laboratories of Molecular Cardiology, Medical College of Virginia, Richmond 23298, USA.
Kontos
M C
MC
Rao
P S
PS
Jesse
R L
RL
Hess
M L
ML
Kukreja
R C
RC
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004578:Electron Spin Resonance Spectroscopy; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D017665:Hydroxyl Radical / Q000032:analysis / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left
D013481:Superoxides; D019335:Nitroarginine; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D001120:Arginine