Hydrogen sulfide interacts with nitric oxide in the heart -Possible involvement of nitroxyl.
Summary of "Hydrogen sulfide interacts with nitric oxide in the heart -Possible involvement of nitroxyl."
Aims The present study aims to investigate the interaction between nitric oxide (NO) and hydrogen sulfide (H(2)S), the two important gaseous mediators in rat hearts. Methods and Results Intracellular calcium in isolated cardiomyocytes was measured with a spectrofluorometric method using fura-2. Myocyte contractility was measured with a video edge system. NaHS (50 muM, an H(2)S donor) had no significant effect on the resting calcium level, electrically-induced calcium transients and cell contractility in ventricular myocytes. Stimulating endogenous NO production with L-arginine or exogenous application of NO donors [sodium nitroprusside (SNP) and 2-(N,N-Diethylamino)-diazenolate-2-oxide (DEA/NO)] decreased myocyte twitch amplitudes accompanied by slower velocities of both cell contraction and relaxation. Surprisingly, NaHS reversed the negative inotropic and lucitropic effects of the above three NO increasing agents. In addition, the mixture of SNP+NaHS increased, whereas SNP alone decreased, the resting calcium level and the amplitudes of electrically-induced calcium transients. Angeli's salt, a nitroxyl anion (HNO) donor, mimicked the effect of SNP+NaHS on calcium handling and myocyte contractility. Three thiols, N-acetyl-cysteine, L-cysteine and glutathione, abolished the effects of HNO and SNP+NaHS on myocyte contraction. Neither Rp-cAMP [100 muM, a protein kinase A (PKA) inhibitor] nor Rp-cGMP ([10 muM, a protein kinase G (PKG) inhibitor]) affected the effects of SNP+NaHS, suggesting a cAMP/PKA or cGMP/PKG independent mechanism. Conclusions H(2)S may interact with NO to form HNO which produces positive inotropic and lusitropic effects. Our findings may shed a light on the interaction of NO and H(2)S and provide new clues to treat cardiovascular diseases.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
This article was published in the following journal.
Name: Cardiovascular research
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Medical and Biotech [MESH] Definitions
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.
A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.