Insulin and insulin-like growth factor-I promotes angiotensinogen production and growth in vascular smooth muscle cells

Background Circulating insulin and insulin-like growth factor-I (IGF-I) lev els are increased in patients with hypertension and insulin resistance. Sin ce both hormones are known to have cell growth-promoting effects, they may contribute to the progression of vascular hypertrophy in patients with insu lin resistance. Insulin-mediated activation of the vascular renin-angiotens in system (RAS) stimulates growth in cultured rat vascular smooth muscle ce lls (VSMC). Objective In order to evaluate the role of IGF-I-mediated activation of com ponents of the tissue RAS, we examined the effect of IGF-I receptor stimula tion on cell proliferation, and production of angiotensinogen in cultured V SMC. Study Design Aortic VSMC were derived from male Sprague-Dawley rats. IGF-I and insulin-mediated DNA synthesis were estimated by H-3-thymidine uptake ( H-3-TdR) with or without the angiotensin I converting enzyme inhibitor, cap topril. Moreover, angiotensinogen released by the cells to the culture medi um was determined by radioimmunoassay with or without the anti-IGF-I recept or antibody alpha IR3 or captopril. Results Both IGF-I and insulin increased 3H-TdR uptake by cultured rat VSMC (P < 0.05). Captopril blocked IGF-I and insulin-mediated 3H-TdR uptake (-3 4.4 +/- 1.9% and -32.7 +/- 1.8%, P < 0.05, respectively). IGF-I increased t he angiotensinogen level in the medium by 30.6 +/- 2.9% (P < 0.01). Insulin also stimulated angiotensinogen synthesis by 26.3 +/- 2.2% (P < 0.01). Cap topril and alpha IR3 significantly suppressed angiotensinogen production st imulated by both IGF-I and insulin. Conclusions These results indicate that IGF-I as well as insulin stimulates angiotensinogen production and growth in VSMC. Thus, both hormones may ind ependently play a role in progression of the vascular hypertrophy and ather osclerosis in patients with hypertension and insulin resistance through act ivation of the tissue PAS. J Hypertens 2000, 18:1051 -1056 (C) Lippincott W illiams & Wilkins.