Hypertension increases insulin-like growth factor binding protein-4 mRNA levels in rat aorta.

Abstract

Insulin-like growth factor-I (IGF-I) is an endocrine and autocrine/paracrine growth factor. Recently, we have demonstrated that interrenal aortic coarctation in the rat increases IGF-I mRNA levels in the thoracic aorta, consistent with a role for this mitogen in hypertensive vascular remodeling. The effects of IGF-I are modulated by several IGF binding proteins including IGFBP-3, the main circulating carrier of IGF-I, and IGFBP-4, the main IGF binding protein produced by vascular smooth muscle cells in vitro. To obtain insights into the regulation of IGF-I and more specifically to study potential changes in IGF binding proteins in high-renin hypertension, we studied male Sprague-Dawley rats that had undergone abdominal aortic coarctation. Compared with sham-operated rats, the study rats showed a rapid increase in IGFBP-4 mRNA levels in the hypertensive (thoracic) aorta, reaching a plateau at 3 days (2.5-fold increase) and persisting for at least 14 days. In striking contrast, IGFBP-4 mRNA decreased slightly in the normotensive (abdominal) aorta at 14 days. IGFBP-3 mRNA levels did not change in either vascular bed after coarctation. Study of hepatic tissue indicated that in coarcted rats IGFBP-4 and IGFBP-3 mRNA levels decreased transiently (approximately 50% at 7 days compared with sham). Circulating IGF-I in coarcted animals decreased slightly (P = .08), and Western ligand analysis indicated that circulating levels of IGF binding proteins were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)