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Hypertension, Vol 22, 214-220, Copyright © 1993 by American Heart Association

ARTICLES

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

JD Peuler, BA Johnson, SM Phare and JR Sowers
Department of Internal Medicine, Wayne State University School of Medicine, VA Medical Center, Detroit, Mich.

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 < .05), with no significant change noted in male rats (+4 mm Hg diastolic). Glyburide increased plasma insulin levels (twofold, P < .04) in female but not in male rats. Glyburide did not affect plasma glucose or catecholamine levels. After incubation with insulin, aortic to rings from glyburide- treated female rats demonstrated more than 40% greater contractile responsiveness the phenylephrine compared with aortic rings from control female rats (P < .04). This insulin-dependent increase in phenylephrine-induced contraction consisted of a reversal in the in vitro action of insulin, from attenuation to accentuation of such contraction (P < .05). This change was not seen in male rats. Neither gender, glyburide, nor insulin influenced acetylcholine-induced relaxation of phenylephrine-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

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