Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats

Abstract

Moore PK. Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats. J Appl Physiol 102: [261][262][263][264][265][266][267][268] 2007. First published October 12, 2006; doi:10.1152/japplphysiol.00096.2006.-The role of hydrogen sulfide (H 2S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H 2S in a rat model of MI in vivo. Animals were randomly divided into three groups (n ϭ 80) and received either vehicle, 14 mol/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 vehicletreated, 40% in PAG-treated, and 27.5% in NaHS-treated (P Ͻ 0.05 vs. vehicle) groups. Infarct size was 52.9 Ϯ 3.5% in vehicle-treated, 62.9 Ϯ 7.6% in PAG-treated, and 43.4 Ϯ 2.8% in NaHS-treated (P Ͻ 0.05 vs. vehicle) groups. Plasma H 2S concentration was significantly increased after MI (59.2 Ϯ 7.16 M) compared with the baseline concentration (i.e., 38.2 Ϯ 2.07 M before MI; P Ͻ 0.05). Elevated plasma H 2S after MI was abolished by treatment of animals with PAG (39.2 Ϯ 5.02 M). We further showed for the first time cystathioninegamma-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 Ϯ 1.2% cell viability in hypoxic vehicle vs. 95 Ϯ 2.3% in nonhypoxic control; P Ͻ 0.05). In conclusion, endogenous H 2 S was cardioprotective in the rat model of MI. PAG reduced endogenous H 2S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H 2S might provide a novel approach to the treatment of MI.cardioprotection; gasomediator; cardiac protection; ischemic animal model FOR MANY YEARS, HYDROGEN SULFIDE (H 2 S) has been considered solely as a broad-spectrum environmental toxicant with effects on many major organ systems, including the lung, brain, and kidney (2, 11). However, the possible physiological role(s) of H 2 S in the cardiovascular system have only recently come to light. It has been suggested that H 2 S interferes with cardiovascular function as a result of anoxia rather than a direct action on cardiac myocytes or vascular smooth muscle cells (13). However, this possibility now appears less certain in light of more recent research. The localization of H 2 S-generating enzymes and the detection of biologically significant levels of H 2 S in plasma and tissue homogenate from animals have recently been reported (20). Endogenous H 2 S is formed locally by the activity of two pyridoxal-5Ј-phosphate-dependent enzymes, namely cystathionine ␤-synthase and cystathionine ␥-lyase (CSE), each of which utilize L-cysteine as substrate (17). Although cystathionine ␤-synthase does not appear to play a major role in generating H 2 S in cardiovasc...

The cardioprotective potential of hydrogen sulfide in myocardial ischemia/reperfusion injury (Review)

“…Other in vitro studies were based on the investigation of isolated rodent hearts using a Langendorff setup (Table III). The H 2 S donor molecule NaHS was used in various ways in the studies; as pretreatment (19,59), as postconditioning (5) or through the whole experiment (60). An experiment with Sprague-Dawley rats used ischemic postconditioning to increase the endogen H 2 S level.…”

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

“…Sen et al (60,61) have also described ameliorative effects of hydrogen sulfide on the progression of kidney disease in rodents with hyperhomocysteinemia. Hydrogen sulfide affords protection to the heart against ischemia-reperfusion injury (5,62), and clinical trials evaluating its therapeutic role in amelioration of ischemic heart disease are underway (44). The mechanisms of cardiac protection may involve diverse pathways and include inhibition of macrophage infiltration of the myocardium, reduction in mitochondrial respiration and preservation of mitochondrial structure, and inhibition of apoptosis (5,61).…”

Vitamin D Up-regulates Glucose Transporter 4 (GLUT4) Translocation and Glucose Utilization Mediated by Cystathionine-γ-lyase (CSE) Activation and H2S Formation in 3T3L1 Adipocytes

“…Results were expressed as relative fluorescence units. H 2 S concentrations in the cell culture supernatant were measured following the formation of methylene blue (17). Briefly, 100 l of medium was mixed with 250 l of 1% (w/v) zinc acetate and 425 l of distilled water, followed by addition of 133 l of N-dimethyl-p-phenylenediamine sulfate (20 mM in 7.2 M HCl) and 133 l of FeCl 3 in (30 mM in 1.2 M HCl) to the test tube.…”