Effects of chronic hypoxia on renal PDGF-A, PDGF-B, and VEGF gene expression in rats

Background: There is evidence from in vitro studies to suggest that the gen es of platelet-derived growth factor (PDGF), and vascular endothelial growt h factor (VEGF) are, like the erythropoietin gene, regulated by oxygen tens ion. Hypoxia-induced stimulation of, for example, PDGF or VEGF might be inv olved in the pathogenesis of acute or chronic renal failure and in renal 'i nflammatory' diseases (glomerulonephritis, vasculitis, allograft rejection) . Methods: Male Wistar rats were exposed to chronic normobaric hypoxia (10% O-2, 90% N-2) for 4 weeks. Additional groups of rats were treated with the endothelin receptor antagonist LU13525 and the NO donor molsidomine. Renal mRNA levels of PDGF-A, PDGF-B, and VEGF were semiquantitated using RNase p rotection assays. Results: Renal gene expression of PDGF-A and PDGF-B was n either affected by 2 or 4 weeks of hypoxia nor by concomitant treatment wit h LU135252 or molsidomine. Chronic hypoxia did also not change VEGF gene ex pression; however, concomitant treatment with LU135252 increased all VEGF s ubtypes (188, 164, 120). Conclusions: The findings of the present study sug gest that renal PDGF and VEGF gene expression in vivo during chronic hypoxi a for 2 and 4 weeks is not sensitive to tissue hypoxia in contrast to cell culture experiments. During chronic hypoxia with concomitant blockade of en dothelin receptors, all VEGF subtypes were increased, suggesting an inhibit ory action of endothelins with regard to renal VEGF gene expression. Copyri ght (C) 2000 S.Karger AG, Basel.