ENDOGENOUS PROTECTION AGAINST REPERFUSION-INDUCED VENTRICULAR-FIBRILLATION - ROLE OF NEURONAL VERSUS NONNEURONAL SOURCES OF NITRIC-OXIDE AND SPECIES DEPENDENCE IN THE RAT VERSUS RABBIT ISOLATED HEART

Nitric oxide (NO) is an endogenous protectant against reperfusion-indu ced Ventricular fibrillation (VF) in the rat isolated heart. Here, the following were investigated: (1) the tissue source of cardioprotectiv e NO using a novel inhibitor (7-nitro indazole; 7-NI) of the neuronal form of NO synthase (NOS) and direct detection of coronary effluent NO by chemiluminescence; and (2) the species dependence by comparing rat and rabbit hearts. Perfusion with modified Krebs solution was followe d by 60 min left regional ischemia and 10 min reperfusion. 7-NI (1 mu M) increased the incidence of VF from 0% to 60% in rat hearts (n = 10; P < 0.05). Co-perfusion with L-arginine (1 mM) reduced VF incidence t o 20% (P: N.S. v controls). The inactive analog of 7-NI (6-amino indaz ole; 6-AI) had no pro-fibrillatory activity. Neither 7-NI nor 6-AI aff ected coronary now or recovery of now during reperfusion. 7-NI reduced basal coronary effluent NO levers to below the limit of detection (<1 pmol), but a massive increase in NO levels occurred when L-arginine w as co-perfused with 7-NI. Although 7-NI had no effect on basal coronar y flow and, by implication, resting NO release, it was found, in separ ate studies, to antagonise substance P-induced vasodilatation and NO r elease, suggesting that its neuronal selectivity is lost in the presen ce of an exogenously administered activator of endothelial NOS in rat hearts. In rabbit hearts, in contrast, 7-NI had no effect on VF or NO levels. However, in rabbit hearts the isozyme non-selective NO synthas e blocker, N-G-nitro-L-arginine methyl ester (L-NAME; 100 mu M), incre ased VF incidence from 0 to 50% (P < 0.05) and, during the first minut e of reperfusion, reduced NO levels from 4929 +/- 893 to 2505 +/- 483 pmol/min/g (P < 0.05) and recovery of coronary flow by 22% (P < 0.05). Each of these effects were prevented by L-arginine co-perfusion. Thes e data indicate a role for basally released NO as an endogenous antifi brillatory cardioprotectant in rat and rabbit isolated heart and indic ate that the tissue source (neuronal in rat but not in rabbit heart) i s species-dependent. (C) 1996 Academic Press Limited