Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase

• Published in: Circulation (New York, N.Y.) N.Y.), 2001-07, Vol.104 (3), p.342-345
• Main Authors: DUPLAIN, Hervé, BURCELIN, Rémy, SCHERRER, Urs, SARTORI, Claudio, COOK, Stéphane, EGLI, Marc, LEPORI, Mattia, VOLLENWEIDER, Peter, PEDRAZZINI, Thierry, NICOD, Pascal, THORENS, Bernard
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Arteries; Biological and medical sciences; Blood and lymphatic vessels; Blood Flow Velocity - drug effects; Blood Flow Velocity - physiology; Blood Glucose - drug effects; Body Weight; Cardiology. Vascular system; Disease Models, Animal; Experimental diseases; Glucose - metabolism; Glucose - pharmacokinetics; Glucose Clamp Technique; Hindlimb - blood supply; Homozygote; Hyperinsulinism - complications; Hyperinsulinism - genetics; Hyperlipidemias - complications; Hyperlipidemias - genetics; Hypertension - complications; Hypertension - genetics; Hypertension, Renovascular - metabolism; In Vitro Techniques; Insulin - pharmacology; Insulin resistance; Insulin Resistance - genetics; Medical sciences; Mice; Mice, Knockout; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Nitrates - blood; Nitric Oxide Synthase - deficiency; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitrites - blood
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.104.3.342

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. 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. 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.