The effects of endothelin-1 and nitric oxide inhibition on myocardial ischemia reperfusion

Nitric oxide (NO) role on myocardial ischemia is not clear although both positive and negative contributions have been reported under different experimental conditions. Our purpose was to investigate the effects of both vasoconstrictors Endothelin-I (ET-1) and Urotensin-II (U-II), NO donor Molsidomin, NO synthase (NOS) inhibitor nitro-Largyninemethylester (L-NAME) iNOS inhibitor L-Canavanine and Anti- Endothelin Receptor Antibody (ET-1.Res.Bl.) on cardiac ischemiareperfusion (I/R) injury. With rat hearts I/R protocol (30 min stabilization, 30 min ischemia, 30 min reperfusion) was introduced. L-NAME, ET-1, U-II, L-Canavanine, Molsidomin and ET-1.Res.Bl. were applied to the groups at the beginning of the ischemia and these groups were compared with the control and continious perfusion groups. Malondialdehid (MDA) and total NO (NOx) levels were measured in reperfusation solutions collected at 1, 5, 10, 20 and 30th minutes. MDA, protein carbonyl groups, reduced glutathion (GSH) and NOx levels were measured at the heart tissue. Left vetricule developed pressure (LVDP), dp/dt maximum(dp/dtmak) and dp/dt minimum (dp/dtmin) were monitored. LVDP levels were decreased in experimental groups. While ET-1 and Molsidomin had a more positive effect on dp/dtmak, NOS inhibition had a negative effect. In all groups dp/dtmin increased while this effect was highest in ET-1.Res.Bl. and Molsidomin and lowest with NOS inhibitors. In ET-1, Molsidomin and U-II groups tissue protein carbonyl, perfusate and tissue NOx and MDA were increased significantly. On the contrary the highest decrease in RSG and GSH was also in these groups. This study demonstrated that ET-1, U-II and external NO increased the oxidative damage and decreased the antioxidant mechanisms.