This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sartori, C. Articles by Scherrer, U. Search for Related Content PubMed PubMed Citation Articles by Sartori, C. Articles by Scherrer, U. Related Collections Autonomic, reflex, and neurohumoral control of circulation Endothelium/vascular type/nitric oxide Other Vascular biology

(Hypertension. 1999;34:586-589.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Effects of Sympathectomy and Nitric Oxide Synthase Inhibition on Vascular Actions of Insulin in Humans

Claudio Sartori; Lionel Trueb; Pascal Nicod; Urs Scherrer

From the Department of Internal Medicine (C.S., P.N., U.S.) and the Botnar Center for Clinical Research, Centre Hospitalier Universitaire Vaudois, and Institute of Physiology (L.T.), University of Lausanne, Switzerland.

Correspondence to Dr Urs Scherrer, Department of Internal Medicine, BH 10.642, CHUV, CH-1011 Lausanne, Switzerland. E-mail Urs.Scherrer{at}chuv.hospvd.ch

Abstract—Insulin exerts cardiovascular actions by stimulating nitric oxide (NO) release and sympathetic neural outflow. It is unclear, however, whether insulin stimulates muscle blood flow (and NO release) by a direct action at the vasculature and/or by stimulating neural vasodilator mechanisms. In these studies we used patients with regional sympathectomy to examine the vascular actions of insulin in the presence and absence of sympathetic vasoconstrictor and vasodilator innervation. A 2-hour insulin (6 pmol/kg per minute)/glucose clamp increased muscle blood flow in both innervated and denervated limbs by roughly 40% (P<0.01 versus baseline for both limbs). The vasodilation reached its maximum within the first 30 to 45 minutes of insulin/glucose infusion in sympathetically denervated limbs, but only at the end of the infusion in innervated limbs (P<0.01, denervated versus innervated limb). Infusion of a NO synthase inhibitor (N^G-monomethyl-L-arginine [L-NMMA]) increased baseline arterial pressure, abolished the vasodilation in the denervated limb, and led to a significant additional increase in arterial pressure during the clamp, but did not alter whole body glucose uptake. Our data indicate that insulin stimulates blood flow in sympathectomized limbs by a direct action at the vasculature. This effect is mediated by stimulation of NO release and appears to be masked by the sympathetic vasoconstrictor tone in innervated limbs.

Key Words: nervous system, sympathetic • insulin • vasodilation • hyperinsulinism • glucose clamp technique • glucose • nitric oxide

This article has been cited by other articles:

				R. Muniyappa, M. Montagnani, K. K. Koh, and M. J. Quon Cardiovascular Actions of Insulin Endocr. Rev., August 1, 2007; 28(5): 463 - 491. [Abstract] [Full Text] [PDF]

				J.-a Kim, M. Montagnani, K. K. Koh, and M. J. Quon Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms Circulation, April 18, 2006; 113(15): 1888 - 1904. [Abstract] [Full Text] [PDF]

				M. Levesque, M. Santure, M. Pitre, A. Nadeau, and H. Bachelard Cholinergic Involvement in Vascular and Glucoregulatory Actions of Insulin in Rats Diabetes, February 1, 2006; 55(2): 398 - 404. [Abstract] [Full Text] [PDF]

				K. Sydow, C. E Mondon, and J. P Cooke Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA Vascular Medicine, May 1, 2005; 10(2_suppl): S35 - S43. [Abstract] [PDF]

				M. Kooijman, G. A. Rongen, P. Smits, and M. T.E. Hopman Preserved {alpha}-Adrenergic Tone in the Leg Vascular Bed of Spinal Cord-Injured Individuals Circulation, November 11, 2003; 108(19): 2361 - 2367. [Abstract] [Full Text] [PDF]

				M. A. Vincent, E. J. Barrett, J. R. Lindner, M. G. Clark, and S. Rattigan Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E123 - E129. [Abstract] [Full Text] [PDF]

				E. C. Eringa, C. D.A. Stehouwer, T. Merlijn, N. Westerhof, and P. Sipkema Physiological concentrations of insulin induce endothelin-mediated vasoconstriction during inhibition of NOS or PI3-kinase in skeletal muscle arterioles Cardiovasc Res, December 1, 2002; 56(3): 464 - 471. [Abstract] [Full Text] [PDF]

				B. F. Jordan, V. Gregoire, R. J. Demeure, P. Sonveaux, O. Feron, J. O'Hara, V. P. Vanhulle, N. Delzenne, and B. Gallez Insulin Increases the Sensitivity of Tumors to Irradiation: Involvement of an Increase in Tumor Oxygenation Mediated by a Nitric Oxide-dependent Decrease of the Tumor Cells Oxygen Consumption Cancer Res., June 1, 2002; 62(12): 3555 - 3561. [Abstract] [Full Text] [PDF]

				N. Charkoudian, J. H. Eisenach, J. L. D. Atkinson, R. D. Fealey, and M. J. Joyner Effects of chronic sympathectomy on locally mediated cutaneous vasodilation in humans J Appl Physiol, February 1, 2002; 92(2): 685 - 690. [Abstract] [Full Text] [PDF]

				C. Rask-Madsen, N. Ihlemann, T. Krarup, E. Christiansen, L. Kober, C. Nervil Kistorp, and C. Torp-Pedersen Insulin Therapy Improves Insulin-Stimulated Endothelial Function in Patients With Type 2 Diabetes and Ischemic Heart Disease Diabetes, November 1, 2001; 50(11): 2611 - 2618. [Abstract] [Full Text] [PDF]

				J. Westerbacka, A. Uosukainen, S. Makimattila, A. Schlenzka, and H. Yki-Jarvinen Insulin-Induced Decrease in Large Artery Stiffness Is Impaired in Uncomplicated Type 1 Diabetes Mellitus Hypertension, May 1, 2000; 35(5): 1043 - 1048. [Abstract] [Full Text] [PDF]