Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats.
The role of hydrogen sulfide (H(2)S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H(2)S in a rat model of MI in vivo. Animals were randomly divided into three groups (n = 80) and received either vehicle, 14 micromol/kg of sodium hydrosulfide (NaHS), or 50 mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment was continued for a further 2 days after MI when the animals were killed. The mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS-treated (P < 0.05 vs. vehicle) groups. Infarct size was 52.9 +/- 3.5% in vehicle-treated, 62.9 +/- 7.6% in PAG-treated, and 43.4 +/- 2.8% in NaHS-treated (P < 0.05 vs. vehicle) groups. Plasma H(2)S concentration was significantly increased after MI (59.2 +/- 7.16 microM) compared with the baseline concentration (i.e., 38.2 +/- 2.07 microM before MI; P < 0.05). Elevated plasma H(2)S after MI was abolished by treatment of animals with PAG (39.2 +/- 5.02 microM). We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining. In the hypoxic vascular smooth muscle cells, we found that cell death was increased under the stimuli of hypoxia but that the increased cell death was attenuated by the pretreatment of NaHS (71 +/- 1.2% cell viability in hypoxic vehicle vs. 95 +/- 2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H(2)S was cardioprotective in the rat model of MI. PAG reduced endogenous H(2)S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H(2)S might provide a novel approach to the treatment of MI.
Zhu
Yi Zhun
YZ
Department of Pharmacology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 117597. phczhuyz@nus.edu.sg
Wang
Zhong Jing
ZJ
Ho
Peiying
P
Loke
Yoke Yun
YY
Zhu
Yi Chun
YC
Huang
Shan Hong
SH
Tan
Chee Sin
CS
Whiteman
Matt
M
Lu
Jia
J
Moore
Philip K
PK
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000032:analysis; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology
D000480:Alkynes; D003470:Culture Media; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D013440:Sulfides; C009055:propargylglycine; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005998:Glycine; D006862:Hydrogen Sulfide