BLOOD-PRESSURE REGULATES PLATELET-DERIVED GROWTH-FACTOR A-CHAIN GENE-EXPRESSION IN VASCULAR SMOOTH-MUSCLE CELLS IN-VIVO - AN AUTOCRINE MECHANISM PROMOTING HYPERTENSIVE VASCULAR HYPERTROPHY

To clarify the role of PDGF A-chain in hypertensive vascular hypertrop hy of spontaneously hypertensive rats (SHRs), we studied levels of PDG F A-chain gene expression and transcription factors related to the gen e in vascular smooth muscle cells (VSMCs) of SHRs in vivo, RNase prote ction assay and in situ hybridization showed that PDGF A-chain mRNA le vels in VSMCs of SHRs were twofold higher than in those of normotensiv e Wistar-Kyoto rats. Gel retardation assays showed that levels of Sp1 and AP-2 in VSMCs of SHRs mere twofold more abundant than in those of Wistar-Kyoto rats. Treatment with four pharmacologically different spe cies of antihypertensive drugs for 2 wk decreased the levels of both P DGF A-chain mRNA and Sp1, but not AP-2 level in VSMCs of SHRs with reg ression of aortic hypertrophy, indicating that increases in levels of both PDGF A-chain mRNA and Sp1 in VSMCs of SHRs were associated with h igh blood pressure. These results suggest that high blood pressure is a stimulus which upregulates PDGF A-chain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular h ypertrophy, and that the activation of the gene may be mediated throug h increases in Sp1 in these cells.