[The roles of vascular endothellial growth factor and endothelin-1 on pulmonary vascular remodelling in rats with hypoxia-induced pulmonary hypertension].
OBJECTIVE
To investigate the roles of the vascular endothelial growth factor(VEGF) and endothelin-1(ET-1) in pulmonary vascular remodelling in rats with hypoxia-induced pulmonary hypertension(HPH) and the effect of pinacidil on VEGF and ET-1 in rats with HPH.


METHODS
46 male Wister rats were divided into three groups i.e. control group, hypoxic group and treated group (hypoxic rats treated with pinacidil for 4 weeks). Rat models with chronic HPH were established by chronic hypobaric hypoxia [(10.0 +/- 0.5)% O2, 4 weeks]. The levels of VEGF and ET-1 in serum and the mean pulmonary arterial pressure (mPAP) and the weight ratio of right ventricle (RV)/left ventricle and septum (LV + S) [RV/(LV + S)] were measured and the small pulmonary arterial morphologic changes were observed with morphometric analysis under microscopes in the three groups.


RESULTS
(1) The levels of VEGF[(118.73 +/- 55.40) ng/L] and ET-1[(221.2 +/- 56.2) ng/L] in serum, mPAP [(28.4 +/- 2.8) mm Hg, 1 mm Hg = 0.133 kPa] and RV/(LV + S) (0.296 +/- 0.033) were significantly higher in the hypoxic group than those in the control group (P < 0.01). Morphometry showed that the external diameter of the small pulmonary arteries became smaller and the ratio of vascular wall thickness to external diameter (MT%) (25.70 +/- 2.58)% and ratio of vascular wall area to total area (MA%) (75.300 +/- 5.600)% significantly increased in the hypoxic group. (2) The levels of VEGF[(78.20 +/- 16.45) ng/L] and ET-1[(181.6 +/- 30.5) ng/L] in serum, mPAP[(23.3 +/- 2.6) mm Hg], RV/(LV + S) (0.266 +/- 0.037), MT%(22.10 +/- 2.51)% and MA% (66.900 +/- 0.061)% significantly decreased in the treated group.


CONCLUSIONS
VEGF and ET-1 play important roles in the development of HPH and pulmonary vascular remodelling. Pinacidil may partly inhibit the development of HPH and pulmonary vascular remodelling by decreasing VEGF and ET-1.
Zhong
X
X
Department of Respiratory Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Liang
G
G
He
Z
Z
D000818:Animals; D016228:Endothelial Growth Factors / Q000097:blood / Q000502:physiology*; D019332:Endothelin-1 / Q000097:blood / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000097:blood* / Q000473:pathology; D008222:Lymphokines / Q000097:blood / Q000502:physiology*; D008297:Male; D011667:Pulmonary Veins / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D019332:Endothelin-1; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors