Effects of different nitric oxide synthases on pulmonary and systemic hemodynamics in hypoxic stress rat model  

作　　者：Huan Zhang Yu Zhang Xiaojun Wang Jie Liu Wei Zhang 

机构地区：[1]Research Center for High Altitude Medicine,Qinghai University,Xining,Qinghai,China [2]Department of Pathology,The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an,Shaanxi,China [3]Department of Basic Medicine,Qinghai University,Xining,Qinghai,China [4]Department of Pathology,Xi'an Chest Hospital,Xi'an,Shaanxi,China

出　　处：《Animal Models and Experimental Medicine》2025年第2期344-352,共9页动物模型与实验医学(英文)

基　　金：This work was supported by the National Natural Science Foundation of China(grant numbers 81560301 and 81160012);the Natural Science Foundation of Qinghai Province(grant number 2022-ZJ-905);‘2022 Qinghai Province Kunlun Talents High-end Innovation and Entrepreneurship Talents’Outstanding Talent Project.

摘　　要：Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.

关 键 词：hypoxic stress nitric oxide synthase peripheral vascular resistance pulmonary vascular resistance 

分 类 号：R594.3[医药卫生—内科学] R-332[医药卫生—临床医学]