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Role of endogenous hydrogen sulfide in pulmonary hypertension induced by lipopolysaccharide

Huang Xinli, Zhou Xiaohong, WEI Peng, Zhang Xiaojing, Meng Xiangyan, Xian Xiaohui

Department of Pathophysiology, Hebei Medical University.Shijiazhuang 050017,Hebei

Abstract

The purpose of the present study was to explore the role of endogenous hydrogen sulfide (H_(2)S) in pulmonary arterialhypertension induced by endotoxin. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group(0.5 mL/kg body weight of normal saline, i.v.), lipopolysaccharide (LPS)-treated group (5 mg/kg body weight of LPS, i.v.), LPS+NaHS(5 mg/kg body weight of LPS, i.v., and 28 #mu#mol/kg body weight of NariS, i.p.) and LPS + PPG group (5 mg/kg body weight of LPS, i.v.,and 30 #mu#mol/kg body weight of PPG, i.p.). Rats were anesthetized with 20% urethane (1 g/kg body weight, i.p.). A polyethylene catheterwas inserted into the pulmonary artery through the fight external jugular vein to measure the mean pulmonary arterial pressure (mPAP)for 7 h, and then the pulmonary artery was isolated rapidly by the method described previously. Pulmonary arterial activity was detected.H_(2)S concentration and cystathionine #gamma#-lyase (CSE) activity in pulmonary artery tissues were determined by biochemical method. CSE mRNA expression was detected by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with control,LPS significantly increased mPAP [(1.82±0.29) kPa vs (l.43±0.26)kPa, P<0.01], decreased H_(2)S production [(26.33±7.84) vs (42.92±8.73)pmol/g wet tissue per minute, P<0.01), and reduced endothelium-dependent relaxation response [(75.72±7.22)% vs (86.40±4.40)%,P<0.01) induced by ACh (1×10~(-6) mol/L). These effects were partly reversed by co-administration of NariS and enhanced by co-administration of PPG. Both CSE activity and CSE mRNA expression were consistent with H_(2)S production. It is suggested that theinhibitory effect of LPS on endothelium-dependent relaxation results in pulmonary hypertension, which might be mediated through H_(2)S.

Key words: Lipopolysaccharide;hydrogen sulfide;Pulmonary hypertension

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Citing This Article：

Huang Xinli, Zhou Xiaohong, WEI Peng, Zhang Xiaojing, Meng Xiangyan, Xian Xiaohui. Role of endogenous hydrogen sulfide in pulmonary hypertension induced by lipopolysaccharide. Acta Physiol Sin 2008; 60 (2): 211-215 (in Chinese with English abstract).