The effect of losartan intervention on the regulation of pulmonary arterial collagen expression by protein kinase C in chronic hypoxic rat models.
OBJECTIVE
To investigate the regulating role of protein kinase C(PKC) and the effects of losartan intervention on the expression of pulmonary arterial collagen in chronic hypoxic rat models.


METHODS
Thirty six rats were randomly divided into three groups: healthy control group(A), hypoxic model group(B),and hypoxic + losartan intervention group (C). MT% (vessel medial thichness/ total thichness) and WA% (vessel wall area/total area) of pulmonary arterioles were measured with light microscopy,the ultrastructures of pulmonary arterioles were observed by electronic microscope, the PKC activities of lung tissues were detected with radioactive method,the protein and(or) mRNA expression of PKC and collagen I, III in arterioles were observed using immunohistochemistry and in situ hybridization. The relative contents [integral light density(LD)] of PKC, collagen I, III and procollagen I, III mRNA in pulmonary arterioles were calculated with image analysor.


RESULTS
(1) The mean pulmonary arterial pressure and weight ratio of right ventricle (RV) to left ventricle(LV)+septum( S)(RV/LV+S) in group B were significantly higher than those in group A(P < 0.01), but in group C they were significantly lower than those in group B (P < 0.01). (2) MT% and WA% of pulmonary arterioles in group B were significantly increased than those in group A (P < 0.01)   while in group C both the parameters were significantly decreased than those in group B (P < 0.01). Collagen fiber deposition in pulmonary arteriolar walls were inhibited in group C by electronic microscopy.(3) The total,cytoplasmic and cytomembrane PKC activities, as well as the ratio of cytomembrane PKC activity to total one in group B were significantly increased than those in group A(P < 0.01),while all these parameters in group C were significantly decreased than those of group B (P < 0.01). (4)LD of PKC,collagen I and procollagen I m RNA expressions in pulmonary arterioles were significantly increased in group B than those in group A(P < 0.01), but in group C they were significantly decreased than those in group B(P < 0.01). There were no significant differences in collagen III and procollagen IIImRNA expressions among the three groups(P > 0.05).(5)Significant positive correlations were found between the PKC activities and collagen I expressions(P < 0.05) and between the expressions of PKC and collagen I in pulmonary arterioles(P < 0.01).


CONCLUSIONS
The PKC signal pathway participated the regulation of pulmonary arterial collagen expression in chronic hypoxic rat models and may play an important role in the pathogenesis of pulmonary hypertension and structural remodeling of pulmonary arterials. Losartan could reduce the hypoxic pulmonary hypertension by interference the role of PKC on pulmonary arterial collagen expression.
Department of Respirology,The First Affilated Hospital, Wenzhou Medical College, Institute of Cor Pulmonale,Wenzhou 325000,China.
Shaoxian
S
Chen
Hao
H
Zhou
Liangxing
L
Wang
Et Al
D000818:Animals; D003094:Collagen; D006976:Hypertension, Pulmonary; D019808:Losartan; D011493:Protein Kinase C; D011651:Pulmonary Artery; D051381:Rats; D017207:Rats, Sprague-Dawley
D003094:Collagen; D011493:Protein Kinase C; D019808:Losartan