Protective effects of vasonatrin peptide against hypobaric hypoxia-induced pulmonary hypertension in rats.
1. The aim of the present study was to investigate the in vivo effects of vasonatrin peptide (VNP) on hypoxia-induced pulmonary hypertension (HPH). 2. The HPH model was developed by subjecting rats to hypobaric hypoxia. The HPH rats were then treated with either VNP (50 microg/kg per day, i.p.) or saline (0.5 mL, i.p.) every day for 7 days. Haemodynamic indices, right ventricular hypertrophy (RVH) and remodelling of the pulmonary arteries were evaluated. In addition, plasma levels of atrial natriuretic peptide (ANP), endothelin (ET)-1 and angiotensin II (AngII) were determined, as was natriuretic peptide receptor-C (NPR-C) mRNA expression in the right ventricle. 3. Hypobaric hypoxia induced severe HPH compared with the normoxic control group. Treatment of HPH rats with VNP for 1 week significantly reduced mean pulmonary arterial pressure, pulmonary vascular resistance, RVH and muscularization of the pulmonary arteries, although pulmonary blood flow was increased in this group. In addition, significantly lower levels of plasma ET-1 and AngII and cardiac NPR-C mRNA expression were observed in VNP-treated compared with saline-treated HPH rats, whereas higher plasma concentrations of ANP were found in the former group. Acute intravenous administration of 50 microg/kg VNP significantly ameliorated pulmonary haemodynamics in HPH rats. 4. Taken together, the date indicate that VNP has certain preventative and therapeutic effects against HPH.
Yu
Jun
J
Center of Teaching Experiment, School of Basic Medical Science, Xi'an.
Feng
Hua-Song
HS
Chen
Bao-Ying
BY
Qu
Ping
P
Liu
Li-Bing
LB
Chen
Jian-Kang
JK
Tie
Ru
R
Huang
Xiao-Jun
XJ
Zhao
Yu-Feng
YF
Zhu
Xiao-Xing
XX
Zhu
Miao-Zhang
MZ
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001274:Atmospheric Pressure; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000473:pathology; D000860:Hypoxia; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism
D000959:Antihypertensive Agents; D019332:Endothelin-1; D000804:Angiotensin II; C068986:ventricular natriuretic peptide, eel; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C