Alleviation effect of intermittent hypobaric hypoxia preconditioning on hypoxic pulmonary artery hypertension and improvement of pulmonary artery vasodilatation in rats

AIM To observe the effect of intermittent hypobaric hypoxia preconditioning on hypoxic pulmonary artery hypertension (HPH) and vasodilatation of pulmonary artery in rats. METHODSTwenty-four male Sprague Dawley rats were randomly divided into control group, HPH group and intermittent hypobaric hypoxia preconditioning group (n=8 in each group). Rats in control group were fed under normal conditions for 10 weeks and rats in HPH group were fed under normal condition with rats in control group for 6 weeks and then HPH models were established by hypoxia method (under condition of hypobaric hypoxia for the following 4 weeks). Rats in intermittent hypobaric hypoxia preconditioning group were pre-conditioned: fed in HPH for 1 week, fed in normal condition for another week, and repeated the process three times (total of 6 weeks). The same HPH models as those in HPH group were then established by hypoxia method (under condition of hypobaric hypoxia for the remaining 4 weeks). Mean pulmonary average pressure (mPAP) and mean right ventricle pressure (mRVP) were measured by right cardiac catheterization, and right ventricle/left ventricle+ventricle spectrum (RV/LV+S) and right ventricle/body weight were weighed. Microstructural development of pulmonary arteriole was observed by hematoxylin-eosin (HE) stained at high magnification and diastolic influence of different acetylcholine and sodium nitroprusside concentrations were observed by preparing a vascular circle from left and right pulmonary trunks by isolated perfusion experiment. RESULTSIn comparison with those in the control group, mPAP, mRVP, RV/(LV+S) and RV/BW in HPH group increased significantly (P<0.01). Histopathological section showed hyperplasia of smooth muscle and elastic fibers, pulmonary and blood vessel wall thickening and vessel narrowing with distortion in HPH group. The relaxation effect of acetylcholine was significantly reduced on HPH conditioned pulmonary vascular rings (P<0.01). In comparison with HPH group, mPAP, mRVP, RV/(LV+S) and RV/BW in intermittent hypobaric hypoxia preconditioned group was markedly reduced (P<0.05). Pathological section showed alleviation of hyperplasia of smooth muscle and elastic fibers, pulmonary and blood vessel wall thickening and vessel narrowing with distortion. The relaxation effect of acetylcholine on pulmonary vascular rings (P<0.05) was significantly increased. CONCLUSIONIntermittent hypobaric hypoxia preconditioning increases the tolerance of pulmonary artery under hypobaric hypoxia environment, alleviates pulmonary artery hypertension and restructuring of right ventricle and improves endothelial function of the pulmonary artery.