Hypoxic Conditioning Suppresses Cytotoxic Nitric Oxide Production Upon Myocardial Reperfusion

Ryou, Myoung-gwi. Hypoxia conditioning suppresses nitric oxide production upon myocardial reperfusion. Master of Science (Integrative Physiology), May 2007, 61pp, 2 tables, 9 figures. This study was conducted in mongrel dogs to test the hypothesis that 20 d normobaric intermittent hypoxic conditioning (IHC) evokes cardioprotective adaptations of the myocardial nitric oxide synthase (NOS) system. Specifically, the proposal that IHC suppresses myocardial NOS activity sufficiently to dampen the cytotoxic burst of NO formation upon reperfusion of ischemic myocardium was tested. Mongrel dogs were conditioned by a 20 d program of IHC (FIO2 9.5-10%; 5-10 min hypoxia/cycle, 5-8 cycles/d with intervening 4 min normoxia). On day 21, ventricular myocardium was sampled for measuring NOS activity (colorimetric assay) and endothelial NOS (eNOS) content (immunoblot). In separate experiments, myocardial nitrite (NO2) release, an stable product of NO oxidation, was measured at baseline and during reperfusion following 1 h occlusion of the left anterior descending coronary artery (LAD). Values in IHC dogs were compared with respective values in non-conditioned, control dogs. IHC lowered left and right ventricular NOS activity by 60%, from 100-115 to 40-45 mU/g protein (P [less than] 0.01), and decreased eNOS content by 30%. IHC dampened cumulative NO2 release during the first 5 min reperfusion from 32 ± 7 to 14 ± 2 μmol/g (P [less than] 0.05), but did not alter hyperemic LAD flow (15 ± 2 vs. 13 ± 2 ml/g). Attenuation of the NOS/NO system may contribute to IHC-induced protection of myocardium from ischemia-reperfusion injury.