Sex-specific effects of an insulin secretagogue in stroke-prone hypertensive rats

Abstract

Glyburide, an insulin secretagogue and an insulin-sensitizing agent, lowers blood pressure in normal male and female dogs when administered acutely. Because insulin resistance may contribute to spontaneous hypertension in rats, we sought to determine if long-term administration of glyburide (5 mg/kg per day by diet, age 5 weeks to 5 months) would lower blood pressure in male and female stroke-prone spontaneously hypertensive rats. Arterial (aortic) rings from these rats were incubated with insulin in vitro (100 mU/mL) 1 hour before and during phenylephrine-induced contraction to determine if long-term glyburide administration improves vascular sensitivity to the intrinsic vasodilator action of insulin. Glyburide, however, significantly increased blood pressures and ratios of heart weight to body weight in 5-month-old female rats (+20 mm Hg diastolic, P