The role of nitric oxide in the cardiac effects of hydrogen peroxide.
Oxidative stress mediated by hydrogen peroxide (H2O2) increases coronary flow (CF) in Langendorff-perfused rat hearts. We investigated the possible role of nitric oxide (NO) in H2O2-induced vasodilation. A dose-response study was conducted to find a concentration of H2O2 which increased CF without influencing left ventricular developed (LVDP) or end-diastolic (LVEDP) pressures. 80(n = 10), 100 (n = 7), 120 (n = 7), 140 (n = 7), 160 (n = 7), and 180 (n = 10) microM H2O2 was infused for 10 min, followed by recovery for 50 min. 80 microM H2O2 increased CF to a maximum of 143 +/- 4 (mean +/- S.E.M) percent of initial value after 15 min observation (p < 0.001 compared to buffer only), with no effect on LVDP or LVEDP. Another series of hearts were perfused with N-nitro-L-Arginine methylester (L-NAME, 1 mM), methylene blue (MB, 50 microM), or haemoglobin (Hb, 10 microM), without (n = 7 in each) or with (n = 10 in each) 80 microM H2O2 for 10 min. L-NAME, MB, and Hb alone increased CF, but attenuated the H2O2-induced increase of CF.LVDP was depressed when L-NAME, MB or Hb were given in conjunction with 80 microM H2O2. In summary, H2O2 concentration-dependently increased LVEDP and depressed LVDP. The H2O2-induced increase of CF was independent of concentration. Inhibition of NO synthesis, action, or soluble guanylate cyclase attenuated the H2O2-induced increase of CF, and depressed LVDP when given together with H2O2. H2O2 induces a NO-dependent vasodilation, and inhibition of NO is detrimental to left ventricular function after H2O2-mediated oxidative stress.
Valen
G
G
Department of Surgery, University Hospital of Tromsø, Norway.
Skjelbakken
T
T
Vaage
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D006454:Hemoglobins; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester