| Abstract: | After vascular endothelial injury, angiotensin II (ANG II) playsa role in the resulting hypertrophic response, and expression ofepidermal growth factor (EGF) is enhanced. Therefore, we tested thepossibility that EGF regulates vascular ANG II action and receptorexpression. Incubation of cultured aortic vascular smooth muscle cells(VSMC) with EGF (or basic fibroblast growth factor but notplatelet-derived growth factor isoforms) resulted inconcentration-dependent (1-50 ng/ml EGF), time-dependent (>8 h),and reversible decreases in ANG II surface receptor density. Forexample, a 50% reduction was observed after exposure to 50 ng/ml EGFfor 24 h. Incubation of cultured VSMC with 50 ng/ml EGF for 24 hresulted in a 77% reduction in ANG II-stimulated inositol phosphateformation. EGF not only prevented but also reversed ANG II receptorupregulation by 100 nM corticosterone. The specifictyrosine kinase inhibitor tyrphostin A48 (50 µM) reducedEGF-stimulated thymidine incorporation and EGF-stimulatedphosphorylation of mitogen-activated protein kinase but did not preventEGF from reducing ANG II receptor density. Neither pertussis toxin (100 ng/ml) nor downregulation of protein kinase C by phorbol myristateacetate (100 nM for 24 h) prevented EGF from reducing ANG II receptordensity. In summary, EGF is a potent negative regulator of vascular ANGII surface receptor density and ANG II action by mechanisms that do notappear to include tyrosine phorphorylation, pertussis toxin-sensitive G proteins, or phorbol ester-sensitive protein kinase C. The possibility that EGF shifts the cell culture phenotype to one that exhibits reducedsurface ANG II density cannot be eliminated by the present studies. |
