Hypertension increases insulin-like growth factor binding protein-4 mRNA levels in rat aorta.
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)
Anwar
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Department of Medicine, Emory University, Atlanta, Ga 30322.
Delafontaine
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D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001017:Aortic Coarctation / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D006439:Hemodynamics; D006973:Hypertension / Q000235:genetics*; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013002:Somatomedins / Q000378:metabolism
D002352:Carrier Proteins; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D003404:Creatinine