Objective：To determine the effect of losartan on chronic cigarette smoke-induced PAH and its possible mechanism. Methods：Rats were randomly divided into four groups according to the factorial design：A group：control；B group：control plus losar－tan；C group：smoke exposure only；D group：smoke exposure plus losartan. The rats in C and D groups were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. After 6 months，right ventriculus systolic pressure（RVSP） was ex－amined. Tissue angiotensin Ⅱ（AngⅡ） levels were measured by iodine-125 radioimmunoassay（RIA） and angiotension converting enzyme 2（ACE2） in lung homogenates were measured by Western blot. Results：Elevated RVSP，thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased AngⅡ and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling，inhibited the smoke-induced RVSP and AngⅡ elevation and partially reversed the ACE2 decrease in rat lungs. Conclusion：The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.
