PMID- 18408142 OWN - NLM STAT- MEDLINE DCOM- 20080708 LR - 20240515 IS - 1535-3702 (Print) IS - 1535-3699 (Electronic) IS - 1535-3699 (Linking) VI - 233 IP - 6 DP - 2008 Jun TI - Hypoxic conditioning suppresses nitric oxide production upon myocardial reperfusion. PG - 766-74 LID - 10.3181/0710-RM-282 [doi] AB - Physiologically modulated concentrations of nitric oxide (NO) are generally beneficial, but excessive NO can injure myocardium by producing cytotoxic peroxynitrite. Recently we reported that intermittent, normobaric hypoxia conditioning (IHC) produced robust cardioprotection against infarction and lethal arrhythmias in a canine model of coronary occlusion-reperfusion. This study tested the hypothesis that IHC suppresses myocardial nitric oxide synthase (NOS) activity and thereby dampens explosive, excessive NO formation upon reperfusion of occluded coronary arteries. Mongrel dogs were conditioned by a 20 d program of IHC (FIO(2) 9.5-10%; 5-10 min hypoxia/cycle, 5-8 cycles/d with intervening 4 min normoxia). One day later, ventricular myocardium was sampled for NOS activity assays, and immunoblot detection of the endothelial NOS isoform (eNOS). In separate experiments, myocardial nitrite (NO(2)(-)) release, an index of NO formation, 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 activities by 60%, from 100-115 to 40-45 mU/g protein (P < 0.01), and decreased eNOS content by 30% (P < 0.05). IHC dampened cumulative NO(2)(-) release during the first 5 min reperfusion from 32 +/- 7 to 14 +/- 2 mumol/g (P < 0.05), but did not alter hyperemic LAD flow (15 +/- 2 vs. 13 +/- 2 ml/g). Thus, IHC suppressed myocardial NOS activity, eNOS content, and excessive NO formation upon reperfusion without compromising reactive hyperemia. Attenuation of the NOS/NO system may contribute to IHC-induced protection of myocardium from ischemia-reperfusion injury. FAU - Ryou, Myoung-Gwi AU - Ryou MG AD - Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA. FAU - Sun, Jie AU - Sun J FAU - Oguayo, Kevin N AU - Oguayo KN FAU - Manukhina, Eugenia B AU - Manukhina EB FAU - Downey, H Fred AU - Downey HF FAU - Mallet, Robert T AU - Mallet RT LA - eng GR - R21 AT003598/AT/NCCIH NIH HHS/United States GR - R01 HL064785/HL/NHLBI NIH HHS/United States GR - HL-071684/HL/NHLBI NIH HHS/United States GR - R01 HL071684/HL/NHLBI NIH HHS/United States GR - AT-003598/AT/NCCIH NIH HHS/United States GR - HL-064785/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20080411 PL - Switzerland TA - Exp Biol Med (Maywood) JT - Experimental biology and medicine (Maywood, N.J.) JID - 100973463 RN - 0 (Hemoglobins) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - Animals MH - Dogs MH - Hematocrit MH - Hemoglobins/metabolism MH - *Hypoxia MH - Ischemia MH - *Myocardial Reperfusion MH - Myocardial Reperfusion Injury MH - Myocardium/*pathology MH - Nitric Oxide/chemistry/*metabolism MH - Nitric Oxide Synthase/*metabolism MH - Nitric Oxide Synthase Type III/metabolism MH - Phosphorylation MH - Reperfusion MH - Time Factors PMC - PMC4462123 MID - NIHMS691026 EDAT- 2008/04/15 09:00 MHDA- 2008/07/09 09:00 PMCR- 2015/06/10 CRDT- 2008/04/15 09:00 PHST- 2008/04/15 09:00 [pubmed] PHST- 2008/07/09 09:00 [medline] PHST- 2008/04/15 09:00 [entrez] PHST- 2015/06/10 00:00 [pmc-release] AID - 0710-RM-282 [pii] AID - 10.3181/0710-RM-282 [doi] PST - ppublish SO - Exp Biol Med (Maywood). 2008 Jun;233(6):766-74. doi: 10.3181/0710-RM-282. Epub 2008 Apr 11.