Nitric oxide synthase inhibition abrogates hydrogen sulfide-induced cardioprotection in mice.

The cardioprotective property of hydrogen sulfide (H(2)S) is recently reported. However, cellular signaling cascades mediated by H(2)S are largely unclear. This study was undertaken to explore the molecular mechanism of H(2)S-induced cardioprotection in mouse heart by utilizing in vivo model of cardiac injury. We report here that intraperitoneal administration of sodium hydrogen sulfide (NaHS, 50 μmol kg(-1 )day(-1) for 2 days), a H(2)S donor, significantly (P ≤ 0.05) increased nitric oxide levels in serum as well as myocardium without any sign of myocardial injury. Typical characteristics of myocardial injury induced by isoproterenol (ISO) administration was significantly (P ≤ 0.05) abrogated by NaHS administration as evidenced from reduction in elevated thiobarbituric acid reactive substances (TBARS) and normalization of glutathione (GSH), glutathione peroxidase, superoxide dismutase (SOD), and catalase activity. Further, decrease in TNF-α expression and improvement in myocardial architecture was also observed. However, co-administration of N-nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor, and Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor along with NaHS and ISO abrogated the beneficial effect of H(2)S differentially. Inhibition of NOS significantly (P ≤ 0.05) increased serum creatine kinase, lactate dehydrogenase, serum glutamic oxaloacetic transaminase activity and myocardial TBARS, along with significant (P ≤ 0.05) reduction of myocardial GSH, SOD, and catalase. This was followed by increase in TNF-α expression and histopathological changes. Our results revealed that H(2)S provides myocardial protection through interaction with NOS and COX-2 pathway and inhibition of NOS completely abrogates the hydrogen sulfide-induced cardioprotection in mice.