Insulin-Mediated Growth in Aortic Smooth Muscle and the Vascular Renin-Angiotensin System

Abstract

Abstract-Insulin has been shown to directly affect blood vessel tone and to promote vascular hypertrophy, but the mechanism of these actions remains uncertain. Because angiotensin I (Ang I)-converting enzyme inhibitors have been shown to improve insulin action and to impede the progression of vascular hypertrophy in hypertensive animal models, it is possible that the vascular properties of insulin may be mediated through the tissue renin-angiotensin system (RAS). To evaluate this relationship, we first investigated the effect of insulin on components of the RAS using cultured rat vascular smooth muscle cells (VSMCs). Insulin treatment (1000 U/mL) markedly increased angiotensinogen mRNA expression and angiotensinogen production. We next investigated the role of the RAS in insulin-mediated cell proliferation, using [ H]thymidine uptake. In summary, insulin induced significant stimulation of angiotensinogen expression and production and stimulated growth similar to that seen with Ang II in cultured rat VSMCs. Inhibition of Ang II production or its binding to the Ang II type 1 (AT 1 ) receptor inhibited insulin-mediated growth in a fashion similar to that seen with inhibition of Ang II-mediated growth. Thus, insulin can modulate the vascular RAS, and the effect of insulin on vascular growth may be via direct effects on angiotensinogen expression and translation operative through both the AT 1 receptor and the conversion of Ang I to Ang II. (Hypertension. 1998;32:482-487.)

ANG II enhances contractile responses via PI3-kinase p110δ pathway in aortas from diabetic rats with systemic hyperinsulinemia

“…Clinical studies in Type 1 diabetic patients have revealed the cardiovascular protection afforded by blockade of the renin-angiotensin system (14). Furthermore, it has been suggested that the actions of insulin on blood vessels, especially its effects on cell growth, may be mediated through activation of the reninangiotensin system (17). Thus we speculated that an increased ANG II level and an abnormality of the PI3-K pathway system might be related to the improvement in vascular contractility previously observed in insulin-treated Type 1 diabetic rats (see above).…”

Vascular Angiotensin Type 1 Receptor Expression Is Associated with Vascular Dysfunction, Oxidative Stress and Inflammation in Fructose-Fed Rats

“…Previous studies from our laboratory have shown that high insulin concentrations can stimulate the RAS and subsequent production of angiotensin II in cultured vascular smooth muscle cells (9,10). A fructose-fed rat study has shown that RAS inhibition with enalapril increases vascular endothelial nitric oxide synthase (eNOS) activity (11), and it can be argued that the angiotensin type 1 receptor (AT1R) is responsible for hypertension (12).…”

Chronic Insulin Infusion Normalizes Blood Pressure and the Gene Expressions of Angiotensin II Type 1 Receptor in Fructose-Fed Rats

“…The hypertension accompanying insulin resistance is most often explained by hyperinsulinemia compensating for the insulin-resistant conditions. Insulin has been hypothesized to stimulate sympathetic nerve activity, sodium absorption in the renal tubules, and proliferation of smooth muscle cells in vessels (1)(2)(3). It remains unclear, however, whether insulin actually increases blood pressure (BP) in vivo.…”