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
A weakly fluorescent complex derived from a binaphthol-benzimidazole ligand was designed and synthesized for hydrogen sulfide at different pH conditions. It was demonstrated that the probe showed the ...
H2S donor molecules have the potential to be viable therapeutic agents. The aim of this current study was (i) to investigate the effects of a novel triphenylphosphonium derivatised dithiolethione (AP3...
Traumatic brain injury (TBI) has been reported to increase the concentration of nitric oxide (NO) in the brain and can lead to loss of cerebrovascular tone; however, the sources, amounts, and conseque...
N-Heterocyclic carbene-stabilized nitric oxide radicals were prepared by direct addition of nitric oxide to two N-heterocyclic carbenes in solution phase. The compounds were fully characterized by X-r...
Nitric oxide (NO) regulation plays a critical role in cardiovascular diseases including heart failure (HF). Markers of NO dysregulation have been found in individuals with depression without cardiovas...
This blinded, placebo-controlled study will administer inhaled nitric oxide to patients undergoing liver transplantation. The purpose of the study is to test if inhaled nitric oxide preven...
A minimum of 100 patients will be enrolled in the study to demonstrate which diagnostic treatment (oxygen or nitric oxide) is most capable of identifying patients with a reactive pulmonary...
The purpose of this study is to determine whether inhaled nitric oxide is an effective treatment for microcirculatory dysfunction and acute organ system failure in the early stage of sepsi...
The purpose of this study is to look at the long term consequences of prematurity in infants treated with inhaled nitric oxide (iNO) while in the neonatal intensive care unit.
The purpose of this study is to assess the safety and efficacy of inhaled nitric oxide in prevention of lung graft dysfunction due to ischemia-reperfusion
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.