| First Author | Zhao X | Year | 2005 |
| Journal | Circulation | Volume | 111 |
| Issue | 22 | Pages | 2966-72 |
| PubMed ID | 15939832 | Mgi Jnum | J:112252 |
| Mgi Id | MGI:3655916 | Doi | 10.1161/CIRCULATIONAHA.104.527226 |
| Citation | Zhao X, et al. (2005) Endothelium-derived nitric oxide regulates postischemic myocardial oxygenation and oxygen consumption by modulation of mitochondrial electron transport. Circulation 111(22):2966-72 |
| abstractText | BACKGROUND: Nitric oxide (NO) production is increased in postischemic myocardium, and NO can control mitochondrial oxygen consumption in vitro. Therefore, we investigated the role of endothelial NO synthase (eNOS)-derived NO on in vivo regulation of oxygen consumption in the postischemic heart. METHODS AND RESULTS: Mice were subjected to 30 minutes of coronary ligation followed by 60 minutes of reperfusion. Myocardial oxygen tension (Po2) was monitored by electron paramagnetic resonance oximetry. In wild-type, N-nitro-L-arginine methyl ester (L-NAME)-treated (with 1 mg/mL in drinking water), and eNOS knockout (eNOS-/-) mice, no difference was observed among baseline myocardial Po2 values (8.6+/-0.7, 10.0+/-1.2, and 10.1+/-1.2 mm Hg, respectively) or those measured at 30 minutes of ischemia (1.4+/-0.6, 2.3+/-0.9, and 3.1+/-1.4 mm Hg, respectively). After reperfusion, myocardial Po2 increased markedly (P<0.001 versus baseline in each group) but was much lower in L-NAME-treated and eNOS-/- mice (17.4+/-1.6 and 20.4+/-1.9 mm Hg) than in wild-type mice (46.5+/-1.7 mm Hg; P<0.001). A transient peak of myocardial Po2 was observed at early reperfusion in wild-type mice. No reactive hyperemia was observed during early reperfusion. Endothelial NO decreased the rate-pressure product (P<0.05), upregulated cytochrome c oxidase (CcO) mRNA expression (P<0.01) with no change in CcO activity, and inhibited NADH dehydrogenase (NADH-DH) activity (P<0.01) without alteration of NADH-DH mRNA expression. Peroxynitrite-mediated tyrosine nitration was higher in hearts from wild-type mice than in eNOS-/- or L-NAME-treated hearts. CONCLUSIONS: eNOS-derived NO markedly suppresses in vivo O2 consumption in the postischemic heart through modulation of mitochondrial respiration based on alterations in enzyme activity and mRNA expression of NADH-DH and CcO. The marked myocardial hyperoxygenation in reperfused myocardium may be a critical factor that triggers postischemic remodeling. |
