VASCULAR REMODELING AND GROWTH-FACTOR GENE-EXPRESSION IN THE RAT LUNGDURING HYPOXIA

Recent studies suggest that the vasoactive peptides endothelin-1 and - 3 and the mitogens VEGF and PDGF-A and -B could be involved in the pat hogenesis of hypoxic pulmonary hypertension. We were interested to inv estigate whether these peptides could also be involved in the vascular remodeling occurring during chronic hypoxia (10% oxygen; 1 and 3 week s) in the rat. Hypoxia increased significantly; systolic right ventric ular pressure and typical morphological signs of vascular remodeling w ere found. This was accompanied by increased ET-1 and the ET-3 mRNA ex pression after acute (6h,P<0.05) and chronic hypoxia of 1(P<0.05) and 3 weeks (P<0.05). In contrast, we found no effects of hypoxia on the g ene expression of VEGF and PDGF-A and -B in the lung. Our findings ind icate that ET-3 in addition to ET-1 could be involved in the process o f hypoxia-induced vascular remodeling, whereas it appears less likely that the mitogens VEGF and PDGF-A and -B are essentially involved in t he pathogenesis of hypoxic pulmonary hypertension.