endothelin-1 and sodium-nitrate

Supplementation with inorganic nitrate has been suggested to be an ergogenic aid for athletes as nitric oxide donor. The purpose of this study was to determine whether ingestion of inorganic sodium nitrate benefits well-trained athletes performing a 40-min exercise test in laboratory conditions. In addition, we investigated the effect of this supplement on plasma levels of endothelin-1 (ET-1) and in nitrated proteins.. Thirteen trained athletes participated in this randomized, double-blind, crossover study. They performed a 40-min cycle ergometer distance-trial test after two 3-d periods of dietary supplementation with sodium nitrate (10 mg·kg of body mass) or placebo.. Concentration of plasma nitrate (256 ± 35 μM) and nitrite (334 ± 86 nM) increased significantly (P < 0.05) after nitrate supplementation compared with placebo (nitrate: 44 ± 11 μM; nitrite: 187 ± 43 nM). In terms of exercise performance, there were no differences in either the mean distance (nitrate: 26.4 ± 1.1 km; placebo: 26.3 ± 1.2 km; P = 0.61) or mean power output (nitrate: 258 ± 28 W; placebo: 257 ± 28 W; P = 0.89) between treatments. Plasma ET-1 increased significantly (P < 0.05) just after exercise in nitrate (4.0 ± 0.8 pg·mL) and placebo (2.4 ± 0.4 pg·mL) conditions. This increase was significantly greater (P < 0.05) in the nitrate group. Levels of nitrated proteins did not differ between treatments (nitrate: preexercise, 91% ± 23%; postexercise, 81% ± 23%; placebo: preexercise, 95% ± 20%; postexercise, 99% ± 19%).. Sodium nitrate supplementation did not improve a 40-min distance-trial performance in endurance athletes. In addition, concentration of plasma ET-1 increased significantly after exercise after supplementation with sodium nitrate.

Topics: Adult; Athletes; Athletic Performance; Bicycling; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Endothelin-1; Humans; Male; Nitrates; Nitric Oxide Donors; Physical Endurance

The objectives of this study were to investigate the vasculoprotective effects of glucose-insulin-potassium (GIK) on ischemia/reperfusion-induced coronary endothelial functional injury and to elucidate the mechanism involved.. Dogs were subjected to 50 min of coronary occlusion and 4 h of reperfusion. Vehicle, GIK, or GK were intravenously infused 5 min before reperfusion, and the coronary vascular dysfunction and endothelial apoptosis were determined. In a separate study, cultured endothelial cells were subjected to simulated ischemia/reperfusion, and the signaling pathway involved in insulin's anti-apoptotic effect was investigated.. In vivo ischemia/reperfusion caused significant coronary vascular endothelial dysfunction as evidenced by reduced endothelium-dependent vasorelaxation, decreased nitric oxide (NO) production, and endothelial cell apoptosis as determined by caspase 3 activation and TUNEL staining. Treatment with GIK, but not GK, markedly improved the endothelium-dependent coronary vasorelaxation (P<0.01 versus vehicle), increased total NO production (P<0.01), and attenuated endothelial apoptosis. In cultured endothelial cells, treatment with insulin also markedly increased NO production and reduced simulated ischemia/reperfusion-induced apoptosis. Moreover, pre-treatment with either Akt inhibitor or NO synthase inhibitor almost abolished the anti-apoptotic effect exerted by insulin but not by SNAP, an NO donor.. These results demonstrate that in vivo treatment with GIK at reperfusion attenuates ischemia/reperfusion-induced coronary endothelial dysfunction and endothelial apoptosis in an Akt-dependent and NO-mediated fashion. The coronary vasculoprotective effect elicited by insulin may contribute to the previously observed cardiac protective effect of GIK.

Topics: Acetylcholine; Animals; Apoptosis; Caspase 3; Caspases; Cells, Cultured; Coronary Vessels; Dogs; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Female; Glucose; Humans; In Situ Nick-End Labeling; In Vitro Techniques; Insulin; Male; Myocardial Reperfusion Injury; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Potassium; Proto-Oncogene Proteins c-akt; Vasodilator Agents