Role of Nitric Oxide Synthase in the Infarct-Limiting Effect of Normobaric Hypoxia

The study was carried out in male Wistar rats. Animals were randomly divided into normoxic control groups and groups exposed to normobaric hypoxia (NH). NH was modeled via 6 consecutive cycles of hypoxia-reoxygenation: normobaric hypoxia (10 min)/reoxygenation (10 min). All animals underwent coronary artery occlusion (45 min) by applying a ligature to the left coronary artery, and reperfusion (2 h) by removing ligature. The following compounds were administered to rats: the non-selective NO-synthase (NOS) inhibitor L-NAME (10 mg/kg i.v.) before NH or 10 min before coronary occlusion; the inducible NOS inhibitor S-methylthiourea (3 mg/kg i.p.) before coronary occlusion; the neuronal NOS inhibitor 7-nitroindazole (50 mg/kg i.v., 10 min) before coronary artery occlusion; a NO donor diethylenetriamine (2 mg/kg i.v. infusion, 5 min) 1 h before coronary artery occlusion. L-NAME and S-methylthiourea completely abolished the infarct-limiting effect of NH. Diethylenetriamine increased cardiac tolerance to ischemia/reperfusion in normoxic control rats. Thus, iNOS plays an important role in the cardioprotective effect of NH.