(Hypertension. 1997;30:1560-1565.)
© 1997 American Heart Association, Inc.
Articles |
Antihypertensive Agent Moxonidine Enhances Muscle Glucose Transport in Insulin-Resistant Rats
From the Muscle Metabolism Laboratory, Department of Physiology, University of Arizona, Tucson (E.J.H., D.L.F., E.Y.B.); the Department of Endocrinology, Eberhard-Karls University, Tübingen, Germany (S.J.); and Lilly Deutschland, Bad Homburg, Germany (J.G.).
Correspondence to Erik J. Henriksen, Department of Physiology, Ina E. Gittings Bldg #93, University of Arizona, Tucson, AZ 85721-0093. E-mail ejhenrik{at}u.arizona.edu
Abstract The sympatholytic antihypertensive agent moxonidine, a centrally acting selective I1-imidazoline receptor modulator (putative agonist), may be beneficial in hypertensive patients with insulin resistance. In the present study, the effects of chronic in vivo moxonidine treatment of obese Zucker rats—a model of severe glucose intolerance, hyperinsulinemia and insulin resistance, and dyslipidemia—on whole-body glucose tolerance, plasma lipids, and insulin-stimulated skeletal muscle glucose transport activity (2-deoxyglucose uptake) were investigated. Moxonidine was administered by gavage for 21 consecutive days at 2, 6, or 10 mg/kg body weight. Body weights in control and moxonidine-treated groups were matched, except at the highest dose, at which final body weight was 17% lower in the moxonidine-treated animals compared with controls. The moxonidine-treated (6 and 10 mg/kg) obese animals had significantly lower fasting plasma levels of insulin (17% and 19%, respectively) and free fatty acids (36% and 28%, respectively), whereas plasma glucose was not altered. During an oral glucose tolerance test, the glucose response (area under the curve) was 47% and 67% lower, respectively, in the two highest moxonidine-treated obese groups. Moreover, glucose transport activity in the isolated epitrochlearis muscle stimulated by a maximally effective insulin dose (13.3 nmol/L) was 39% and 70% greater in the 6 and 10 mg/kg moxonidine-treated groups, respectively (P<.05 for all effects). No significant alterations in muscle glucose transport were elicited by 2 mg/kg moxonidine. These findings indicate that in the severely insulin-resistant and dyslipidemic obese Zucker rat, chronic in vivo treatment with moxonidine can significantly improve, in a dose-dependent manner, whole-body glucose tolerance, possibly as a result of enhanced insulin-stimulated skeletal muscle glucose transport activity and reduced circulating free fatty acids.
Key Words: sympatholytics • glucose tolerance test • imidazoline receptor modulation
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