LOSS OF PACING-INDUCED PRECONDITIONING IN RAT HEARTS - ROLE OF NITRIC-OXIDE AND CHOLESTEROL-ENRICHED DIET

We examined whether the inhibition of nitric oxide (NO) synthesis by N -G-nitro-L-arginine (LNNA) abolished pacing-induced preconditioning, a nd if prolonged exposure to cholesterol-enriched diet led to the loss of preconditioning due to decreased cardiac NO formation. Therefore, W istar rats fed 2% cholesterol-enriched diet or standard diet for 24 we eks were treated with a single dose of 1 mg/kg LNNA or its solvent at the end of the week 24, respectively. Isolated hearts from all groups were subjected to either preconditioning induced by three consecutive periods of pacing at 600 beats/min for 5 min, with 5-min interpacing p eriods, or time-matched non-preconditioning perfusion, followed by a 1 0-min coronary occlusion, respectively. In the control group, coronary occlusion after a non-preconditioning protocol decreased aortic flow (AF) from 45.4 +/- 2.4 to 15.6 +/- 1.5 ml/min, and resulted in a lacta te dehydrogenase (LDH) release of 219 +/- 5 5 mU/min/g, however, preco nditioning attenuated the consequences of coronary occlusion [AF: 27.3 +/- 1.7 ml/min (P<0.05); LDH: 44 +/- 14 mU/min/g (P<0.05)]. Precondit ioning did not confer protection in the LNNA-treated (AF: 17.4 +/- 1.5 ml/min; LDH: 151 +/- 21 mU/min/g), and/or in the high-cholesterol-fed groups (AF: 15.7 +/- 1.2 ml/min; LDH: 168 +/- 22 mU/min/g). Precondit ioning was preserved however, when hearts were treated with LNNA after the preconditioning protocol [RF: 29.6 +/- 2.2 ml/min (P<0.05): LDH: 48 +/- 17 mU/min/g (P<0.05)]. Both LNNA treatment and cholesterol-enri ched diet markedly decreased cardiac NO content assayed by electron sp in resonance spectroscopy. We conclude that NO may be involved in the triggering mechanism of pacing-induced preconditioning, the protective effect of which is blocked by sustained exposure to dietary cholester ol, possibly by influencing cardiac metabolism of NO. (C) 1997 Academi c Press Limited.