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(Circulation. 2001;104:342.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Insulin Resistance, Hyperlipidemia, and Hypertension in Mice Lacking Endothelial Nitric Oxide Synthase
From the Department of Internal Medicine and the Botnar Center for Clinical Research (H.D., C.S., S.C., M.E., M.L., P.V., P.N., U.S.) and the Division of Hypertension and Vascular Medicine (T.P.), Centre Hospitalier Universitaire Vaudois, and the Institute of Pharmacology and Toxicology, University of Lausanne (R.B., B.T.), Lausanne, Switzerland.
Correspondence to Dr Urs Scherrer, Department of Internal Medicine, BH 10.642, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland. E-mail urs.scherrer{at}chuv.hospvd.ch
Background— Insulin resistance and arterial hypertension are related, but the underlying mechanism is unknown. Endothelial nitric oxide synthase (eNOS) is expressed in skeletal muscle, where it may govern metabolic processes, and in the vascular endothelium, where it regulates arterial pressure.
Methods and Results— To study the role of eNOS in the control of the metabolic action of insulin, we assessed insulin sensitivity in conscious mice with disruption of the gene encoding for eNOS. eNOS-/- mice were hypertensive and had fasting hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose uptake than control mice. Insulin resistance in eNOS-/- mice was related specifically to impaired NO synthesis, because in equally hypertensive 1-kidney/1-clip mice (a model of renovascular hypertension), insulin-stimulated glucose uptake was normal.
Conclusions— These results indicate that eNOS is important for the control not only of arterial pressure but also of glucose and lipid homeostasis. A single gene defect, eNOS deficiency, may represent the link between metabolic and cardiovascular disease.
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