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ENDOCRINE AND REPRODUCTIVE

Contrasting Metabolic Effects of Antihypertensive Agents

Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio

Hypertension often coexists with hyperlipidemia, insulin resistance, and glucose intolerance, a comorbidity known as metabolic syndrome X. Different antihypertensives have mixed effects on these associated abnormalities. We compared three antihypertensives in the spontaneously hypertensive obese rat model of syndrome X. Moxonidine (4 mg/kg), an imidazoline and ₂-adrenergic agonist, -methyldopa (200 mg/kg), an ₂-adrenergic agonist, or the vasodilator hydralazine (10 mg/kg) was given orally for 15 d. All three agents lowered blood pressure equally. Moxonidine significantly reduced fasting plasma insulin, glucagon, cholesterol, triglycerides, and free fatty acids (FFA) compared with untreated controls. In contrast, syndrome X markers were not affected by -methyldopa treatment, and hydralazine reduced only glucagon and FFA. Relative to untreated controls, moxonidine improved glucose tolerance as shown by reduced glucose area under the curve (AUC) (13.6 ± 2.4 versus 42.5 ± 9.9 g · min/dl). Insulin AUC was increased (7.4 ± 0.9 versus 3.9 ± 1.8 µg · min/ml) as was the plasma C-peptide response to the glucose load. In contrast, -methyldopa and hydralazine worsened glucose tolerance (68 ± 26 and 110 ± 21 g · min/ml, respectively) and significantly reduced insulin AUC (2.5 ± 0.8 and –2.3 ± 1.0 µg · min/ml, respectively) compared with controls. Moxonidine reduced but -methyldopa and hydralazine elevated glucagon levels after the glucose load. Contrary to the "hemodynamic hypothesis" for the metabolic actions of antihypertensives, which predicts roughly equal benefits, only moxonidine had a positive impact on comorbidities. This unique action suggests a role for direct stimulation of imidazoline receptors.

Address correspondence to: Dr. Paul Ernsberger, Department of Nutrition, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106-4906. E-mail: pre{at}po.cwru.edu

This article has been cited by other articles:

				Z. Sun and P. Ernsberger Marked Insulin Resistance in Obese Spontaneously Hypertensive Rat Adipocytes Is Ameliorated by in Vivo but Not in Vitro Treatment with Moxonidine J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 845 - 852. [Abstract] [Full Text] [PDF]

				R. A. Velliquette, J. E. Friedman, J. Shao, B. B. Zhang, and P. Ernsberger Therapeutic Actions of an Insulin Receptor Activator and a Novel Peroxisome Proliferator-Activated Receptor {gamma} Agonist in the Spontaneously Hypertensive Obese Rat Model of Metabolic Syndrome X J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 422 - 430. [Abstract] [Full Text] [PDF]

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