[The regulation of carbon monoxide/heme oxygenase system by hydrogen sulfide in rats with hypoxic pulmonary hypertension].
OBJECTIVE
To explore the impact of hydrogen sulfide (H2S) on the carbon monoxide (CO)/heme oxygenase-1 (HO-1) system in pulmonary artery of hypoxic rats.


METHODS
Twenty-seven rats were randomly divided into four groups: hypoxic group (n = 7), hypoxic + NaHS group (n = 7), hypoxic + propargylglycine (PPG) group (n = 6) and control group (n = 7). After 21 days, pulmonary artery mean pressure (mPAP) of each rat was evaluated and the plasma concentration of H2S and CO were measured. The expression of HO-1 in pulmonary arteries of each rat was detected by immunohistochemistry technique. In situ hybridization for HO-1 mRNA in pulmonary arteries was also observed.


RESULTS
mPAP was significantly increased in hypoxic rats [(20.5 +/- 2.9) mm Hg] as compared with that of normal controls [(14.8 +/- 3.6) mm Hg, P <0.05]. The plasma H2S[(196+/-22 ) micromol/L] of hypoxic group was decreased significantly compared with control group [(294+/-26) micromol/L, P < 0. 05]. The plasma CO and the expression of HO-1 protein and mRNA in large, medium and small sized pulmonary arteries of hypoxic group [ (0.348 +/- 0.021) micromol/L, 0.79+/-0.08, 0.77+/-0.08, 0.76+/-0.09, 0.813+/-0.052, 0.831+/-0.043, 0.819+/-0.032, respectively] were significantly increased compared to control rats [(0.313+/-0. 020) micromol/L, 0.66+/-0.08, 0.64+/-0.05, 0.54+/-0.05; 0.573 +/- 0.148, 0.532+/-0.131, 0.473+/-0.102, respectively; all P <0.05]. Compared with hypoxic group, the plasma H2S of hypoxic + NaHS group [(324+/-33 ) micromol/L] was significantly increased, and mPAP was decreased significantly (all P < 0.05). Meanwhile, compared with hypoxic group, the plasma concentration of CO [(0.393+/-0.032) micromol/L], the expression of HO-1 protein and mRNA in large, medium and small sized pulmonary arteries were significantly increased in hypoxic + NaHS group (0.88+/-0.04, 0.89 +/- 0.05, 0.89 +/- 0.06; 0.913 +/- 0.022, 0.922 +/- 0.021, 0.933 +/- 0.014, respectively; all P < 0.05). However, compared with hypoxic group, the plasma concentration of H2S was decreased significantly in hypoxic + PPG group [(142 +/- 45) micromol/L, P < 0. 05], and mPAP was increased significantly (P < 0.05). With the decrease of H2S in hypoxic + PPG group, the plasma concentration of CO, the expression of HO-1 protein and mRNA in large, medium and small sized pulmonary arteries were significantly decreased [(0.274 +/- 0.032) micromol/L; 0.54 +/- 0.06, 0.56+/-0.04, 0.39+/-0.06; 0.423 +/- 0.043, 0.418 +/- 0.091, 0.382+/-0.051 respectively; all P <0.05] compared to hypoxic group.


CONCLUSIONS
H2S upregulated CO/HO-1 system in pulmonary arteries of hypoxic rats.
Zhang
Qing-you
QY
Department of Pediatrics, First Hospital, Peking University, Beijing, China.
Du
Jun-bao
JB
Zhang
Chun-yu
CY
Tang
Chao-shu
CS
D000818:Animals; D002248:Carbon Monoxide / Q000097:blood*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D006862:Hydrogen Sulfide