Journal of Applied Physiology AJP: Endocrinology and Metabolism
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J Appl Physiol 93: 1770-1778, 2002; doi:10.1152/japplphysiol.00500.2002
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Vol. 93, Issue 5, 1770-1778, November 2002

Dexfenfluramine protects against pulmonary hypertension in rats

Yoshihide Mitani1, Asuman Mutlu1, James C. Russell2, David N. Brindley2, John DeAlmeida1, and Marlene Rabinovitch1,3

1 Division of Cardiovascular Research/Department of Laboratory Medicine and Pathobiology, The Hospital for Sick Children/University of Toronto, Toronto, Ontario M5G1X8; 2 Departments of Surgery and Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G2S2; and 3 Stanford University School of Medicine, Stanford, California 94305-5162

Dexfenfluramine (Dex), an appetite suppressant and serotonin reuptake inhibitor, is associated with pulmonary vascular disease (PVD) in some patients. The variability might be related to undetermined genetic abnormalities interacting with factors such as gender, weight loss, and vascular injury. We, therefore, assessed the effect of Dex (5 mg · kg-1 · day-1) in female obese rats, designated JCR:LA-cp or cp/cp; in lean rats, designated (+/?); and in normal Sprague-Dawley (S-D) rats under control conditions or after endothelial injury induced by monocrotaline (60 mg/kg). Pulmonary arterial pressure, right ventricular hypertrophy, percent medial wall thickness of muscular arteries, and muscularization of peripheral arteries were assessed as indexes of PVD. Although Dex reduced weight gain in cp/cp and S-D rats (P < 0.05 for both), it did not cause PVD. Moreover, PVD in S-D rats after monocrotaline injection was paradoxically ameliorated by Dex (P < 0.05) despite induction of pulmonary artery elastase (P < 0.05), which we showed is critical in inducing experimental PVD. Thus it is possible that Dex is concomitantly offsetting the sequelae of elastase activity.

pulmonary heart disease; obesity; nitric oxide


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