Attenuation of insulin-mediated pressor effect and nitric oxide release in rats with fructose-induced insulin resistance

Hyperinsulinemia and insulin resistance frequently coexist and have been implicated in the pathogenesis of hypertension. This study aimed to identify the specific effect of hyperinsulinemia on blood pressure and nitric oxide (NO) release in fructose-induced hyperinsulinemic, insulin-resistant rats. Male Sprague-Dawley rats were fed either standard chow or a 60% fructose-enriched diet for 8 weeks before acute study. After basal period, somatostatin (1.3 mug/kg/min) and a variable glucose infusion (to maintain euglycemia) were given intravenously to all groups of rats. In control rats (C) and fructose-fed rats (F) with insulin infusion, insulin (4 mU/kg/min) was given to create a similar hyperinsulinemic condition. In C and F without insulin infusion, a vehicle instead of insulin was infused to produce a hypoinsulinemic state. In C, somatostatin reduced plasma insulin level but did not alter mean arterial pressure (MAP) and heart rate. Insulin infusion significantly increased MAP and NOx (sum of nitrate and nitrite) levels after 90 min and thereafter the elevated MAP and NOx responses were sustained throughout the study. In the basal period, F exhibited significantly higher MAP and plasma insulin levels than C. The index of insulin sensitivity (M) was significantly lower in F than in C with insulin infusion. Somatostatin significantly reduced plasma insulin level but did not affect MAP and NOx level in F. The stimulatory effects of insulin on MAP and NO levels were significantly smaller in F than in C. In conclusion, acute insulin-induced pressor response and NO release were attenuated in rats with fructose-treated insulin resistance, suggesting that hyperinsulinemia-associated attenuation of NO production contributes, at least partly, to the development of fructose-induced hypertension in rats. (C) 2004 American Journal of Hypertension, Ltd.