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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) levels are increased in patients with hypertension and insulin resistance. Since both hormones are known to have cell growth-promoting effects, they may contribute to the progression of vascular hypertrophy in patients with insulin resistance. Insulin-mediated activation of the vascular renin–angiotensin system (RAS) stimulates growth in cultured rat vascular smooth muscle cells (VSMC). Objective In order to evaluate the role of IGF-I-mediated activation of components of the tissue RAS, we examined the effect of IGF-I receptor stimulation on cell proliferation, and production of angiotensinogen in cultured VSMC. Study Design Aortic VSMC were derived from male Sprague-Dawley rats. IGF-I and insulin-mediated DNA synthesis were estimated by 3 H-thymidine uptake (3H-TdR) with or without the angiotensin I converting enzyme inhibitor, captopril. Moreover, angiotensinogen released by the cells to the culture medium was determined by radioimmunoassay with or without the anti-IGF-I receptor antibody αIR3 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 (−34.4 ± 1.9% and −32.7 ± 1.8%, P < 0.05, respectively). IGF-I increased the 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). Captopril and αIR3 significantly suppressed angiotensinogen production stimulated 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 independently play a role in progression of the vascular hypertrophy and atherosclerosis in patients with hypertension and insulin resistance through activation of the tissue RAS.