Hydrogen sulfide interacts with nitric oxide in the heart: possible involvement of nitroxyl.
OBJECTIVE
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.


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 µM, an H(2)S donor) had no significant effect on the resting calcium level, electrically induced (EI) 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] decreased myocyte twitch amplitudes accompanied by slower velocities of both cell contraction and relaxation. Surprisingly, NaHS reversed the negative inotropic and lusitropic 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 EI 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 [a protein kinase A (PKA) inhibitor] nor Rp-cGMP [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 a thiol sensitive molecule (probably HNO) which produces positive inotropic and lusitropic effects. Our findings may shed light on the interaction of NO and H(2)S and provide new clues to treat cardiovascular diseases.
Yong
Qian-Chen
QC
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 18 Medical Drive, MD2, 117597, Singapore, Singapore.
Hu
Li-Fang
LF
Wang
Suhua
S
Huang
Dejian
D
Bian
Jin-Song
JS
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004048:Diethylamines / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004048:Diethylamines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D009599:Nitroprusside; D009569:Nitric Oxide; D002110:Caffeine; C087229:diethylamine dinitric oxide adduct; D000242:Cyclic AMP; C039900:nitroxyl; D006152:Cyclic GMP; D002118:Calcium; D006862:Hydrogen Sulfide