Sex-specific effects of an insulin secretagogue in stroke-prone hypertensive rats.
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)
Peuler
J D
JD
Department of Internal Medicine, Wayne State University School of Medicine, VA Medical Center, Detroit, Mich.
Johnson
B A
BA
Phare
S M
SM
Sowers
J R
JR
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics* / Q000378:metabolism*; D012727:Sex Characteristics; D014661:Vasoconstriction / Q000187:drug effects
D007328:Insulin; D010656:Phenylephrine; D005905:Glyburide