Vasodilation effect and its mechanism of C1q/TNF-related-protein-9 on pulmonary arteries of hypoxic pulmonary hypertensive rat

AIM To observe the vasodilation effects of CTRP9 on isolated rat pulmonary arteries from hypoxic pulmonary hypertension( HPH) rats and to investigate the potential molecular mechanisms. METHODS Twenty-four male Sprague Dawley( SD) rats were randomly grouped by eight each for control group,HPH 2-week group and HPH 4-week group. SD rats in the control group were fed under normal conditions,and HPH models in HPH groups were established by hypoxia method. Mean pulmonary average pressure( m PAP) and mean right ventricle pressure( mRVP) were measured by right cardiac catheterization,right ventricle / left ventricle + ventricular septum RV /( LV + S) and right ventricle /body weight were weighed. Levels of serum NO and CTRP9 were gauged by ELISA method. Microstructure development of pulmonary arteriole was observed by hematoxylin-eosin( HE) staining at high magnification and diastolic influence of different CTRP9 concentrations was observed by preparing vascular circles from left and right pulmonary trunks by isolated perfusion experiment. Perfusion liquid from affected vascular rings was collected to detect NO content and rest of pulmonary vascular tissue was collected and grouped to incubate with different levels of CTRP9,and p AMPK / AMPK,p Akt / Akt and pe NOS / e NOS were measured by Western blot after Compound C or L-NAME was added into some HPH groups prior to incubation. RESULTS In comparison with those in the control group,m PAP,mRVP,RV /( LV + S) and RV / BW in HPH groups increased significantly( P < 0. 01) and levels of serum NO and CTRP9 decreased( P < 0. 05,P < 0. 01). Pathological section showed hyperplasia of smooth muscle and elastic fibers,pulmonary and blood vessel wall thickening and vessel narrowing with distortion in HPH groups. Significant relaxation effect was observed from CTRP9 influenced vascular rings,which had good relaxation responses to acetylcholine and sodium nitroprusside. But the relaxation effect was inhibited by Compound C or L-NAME pretreatment. Perfusate NO product increased in CTRP9 influenced vessel tissues( P < 0. 05). Significant increases of p AMPK / AMPK,p Akt / Akt and pe NOS / e NOS in CTRP incubated vessel tissues were observed. CONCLUSION Vascular endothelial dysfunction existed when HPH,CTRP9 has a remarkable vasodilation effect.