Defective nitric oxide synthesis: a link between metabolic insulin resistance, sympathetic overactivity and cardiovascular morbidity

Department of Internal Medicine and Botnar Centre for Clinical Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Urs.Scherrer@chuv.hospvd.ch

Epidemiological studies demonstrate an association between insulin resistance, hypertension and cardiovascular morbidity. In addition to its metabolic effects, insulin also has important cardiovascular actions. The sympathetic nervous system and the nitric oxide-l-arginine pathway have emerged as central players in the mediation of these actions. Over the past decade, the underlying mechanisms and the factors that may govern the interaction between insulin and these two major cardiovascular regulatory systems have been studied extensively in healthy people and insulin-resistant individuals. Here we summarize the current understanding and gaps in knowledge on these interactions. We propose that a genetic and/or acquired defect of nitric oxide synthesis could represent a central defect triggering many of the metabolic, vascular and sympathetic abnormalities characteristic of insulin-resistant states, all of which may predispose to cardiovascular disease.

This article has been cited by other articles:

				G. Murdolo, M. Sjostrand, L. Strindberg, S. Gudbjornsdottir, L. Lind, P. Lonnroth, and P.-A. Jansson Effects of Intrabrachial Metacholine Infusion on Muscle Capillary Recruitment and Forearm Glucose Uptake during Physiological Hyperinsulinemia in Obese, Insulin-Resistant Individuals J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2764 - 2773. [Abstract] [Full Text] [PDF]

				E. Mata-Greenwood and D.-B. Chen Racial Differences in Nitric Oxide--Dependent Vasorelaxation Reproductive Sciences, January 1, 2008; 15(1): 9 - 25. [Abstract] [PDF]

				P. J. Pagano and D. D. Gutterman The adventitia: The outs and ins of vascular disease Cardiovasc Res, September 1, 2007; 75(4): 636 - 639. [Full Text] [PDF]

				S. Thalmann and C. A. Meier Local adipose tissue depots as cardiovascular risk factors Cardiovasc Res, September 1, 2007; 75(4): 690 - 701. [Abstract] [Full Text] [PDF]

				F. Iellamo, M. Tesauro, S. Rizza, S. Aquilani, C. Cardillo, M. Iantorno, M. Turriziani, and R. Lauro Concomitant Impairment in Endothelial Function and Neural Cardiovascular Regulation in Offspring of Type 2 Diabetic Subjects Hypertension, September 1, 2006; 48(3): 418 - 423. [Abstract] [Full Text] [PDF]

				E. C. Eringa, C. D. A. Stehouwer, K. Walburg, A. D. Clark, G. P. van Nieuw Amerongen, N. Westerhof, and P. Sipkema Physiological Concentrations of Insulin Induce Endothelin-Dependent Vasoconstriction of Skeletal Muscle Resistance Arteries in the Presence of Tumor Necrosis Factor-{alpha} Dependence on c-Jun N-Terminal Kinase Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 274 - 280. [Abstract] [Full Text] [PDF]

				C. K. Roberts and R. J. Barnard Effects of exercise and diet on chronic disease J Appl Physiol, January 1, 2005; 98(1): 3 - 30. [Abstract] [Full Text] [PDF]

				S. Cook, O. Hugli, M. Egli, B. Menard, S. Thalmann, C. Sartori, C. Perrin, P. Nicod, B. Thorens, P. Vollenweider, et al. Partial Gene Deletion of Endothelial Nitric Oxide Synthase Predisposes to Exaggerated High-Fat Diet--Induced Insulin Resistance and Arterial Hypertension Diabetes, August 1, 2004; 53(8): 2067 - 2072. [Abstract] [Full Text] [PDF]

				K. F. Harris and K. A. Matthews Interactions Between Autonomic Nervous System Activity and Endothelial Function: A Model for the Development of Cardiovascular Disease Psychosom Med, March 1, 2004; 66(2): 153 - 164. [Abstract] [Full Text] [PDF]

				K. J. Stewart Exercise Training and the Cardiovascular Consequences of Type 2 Diabetes and Hypertension: Plausible Mechanisms for Improving Cardiovascular Health JAMA, October 2, 2002; 288(13): 1622 - 1631. [Abstract] [Full Text] [PDF]

				H. Duplain, R. Burcelin, C. Sartori, S. Cook, M. Egli, M. Lepori, P. Vollenweider, T. Pedrazzini, P. Nicod, B. Thorens, et al. Insulin Resistance, Hyperlipidemia, and Hypertension in Mice Lacking Endothelial Nitric Oxide SynthaseNote Added in Proof Circulation, July 17, 2001; 104(3): 342 - 345. [Abstract] [Full Text] [PDF]