ABDOMINAL COARCTATION INCREASES INSULIN-LIKE GROWTH FACTOR-I MESSENGER-RNA LEVELS IN RAT AORTA

We have previously demonstrated specific insulin-like growth factor I (IGF I) mRNA transcripts in cultured endothelial and vascular smooth muscle cells and postulated an important role for IGF I in blood vessel growth responses. The purpose of this study was to characterize IGF I gene expression in a model of aortic coarctation hypertension in the rat. This high-renin model of hypertension is associated with hyperplastic vascular responses. Northern analysis of rat aorta demonstrated four specific IGF I mRNA transcripts sized 7.6, 4.6, 1.8, and 0.9-1.2 kb. Quantitation of aortic IGF I mRNA levels by solution hybridization/RNase protection assay demonstrated induction of IGF I transcripts in the hypertensive aorta; levels more than doubled at 7 days and were still significantly elevated 21 days after coarctation. In situ hybridization analysis indicated that IGF I transcripts were localized primarily to adventitial surfaces in normotensive aorta, with minimal signal detected over vascular cells. In hypertensive aortas, there was an increase in IGF I transcripts primarily over vascular smooth muscle cells. Thus, vascular IGF I gene expression is induced in this model of high-renin hypertension. IGF I may play an important role in autocrine/paracrine-mediated vessel wall remodeling in hypertension.