This Article Full Text Full Text (PDF) All Versions of this Article: 109/1/47    most recent 01.CIR.0000105681.70455.73v1 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 Ardilouze, J.-L. Articles by Karpe, F. Search for Related Content PubMed PubMed Citation Articles by Ardilouze, J.-L. Articles by Karpe, F. Related Collections Autonomic, reflex, and neurohumoral control of circulation Endothelium/vascular type/nitric oxide

(Circulation. 2004;109:47-52.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Nitric Oxide and ß-Adrenergic Stimulation Are Major Regulators of Preprandial and Postprandial Subcutaneous Adipose Tissue Blood Flow in Humans

Jean-Luc Ardilouze, MD; Barbara A. Fielding, PhD; Jenny M. Currie, BSc; Keith N. Frayn, PhD, ScD; Fredrik Karpe, MD, PhD

From the Oxford Centre for Diabetes, Endocrinology, and Metabolism, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.

Correspondence to Dr F. Karpe, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Oxford OX3 7LJ, UK. E-mail fredrik.karpe{at}oxlip.ox.ac.uk

Received May 13, 2003; de novo received July 16, 2003; revision received September 4, 2003; accepted September 8, 2003.

Background— Blood flow mediates the metabolic and endocrine roles of adipose tissue. We have previously shown that the postprandial adipose tissue blood flow (ATBF) increase is dependent on insulin sensitivity. However, subcutaneous local insulin delivery had no demonstrable effect on either preprandial or postprandial ATBF. We hypothesized that insulin may act indirectly via sympathetic activation, mainly in the postprandial period, and that nitric oxide may be an overall major regulator of subcutaneous ATBF.

Methods and Results— We investigated the endogenous preprandial and postprandial regulation of ATBF by applying local tissue blockade of ß-adrenergic (propranolol), -adrenergic (phentolamine and yohimbine), and nitric oxide (N^G-monomethyl-L-arginine, L-NMMA) regulation of blood flow. Healthy subjects (body mass index, 18 to 31 kg/m²) were challenged with 75 g glucose for endogenous stimulation of ATBF. We used the novel "microinfusion" technique, which allows for simultaneous local delivery of pharmacological agents (or contralateral saline) and measurement of ATBF with the ¹³³Xe washout method. Compared with control, the preprandial ATBF was not affected by propranolol but was increased by 21% (P<0.013) and 15% (P=0.004) with phentolamine and yohimbine, respectively. A decrease of 42% (2.97±0.33 versus 4.75±0.47 mL · min^-1 · 100 g tissue^-1, P<0.01) was seen with L-NMMA. The postprandial response was blunted by 58% (0.81±0.42 versus 1.90±0.44 mL · min^-1 · 100 g tissue^-1, P<0.004) with propranolol, but neither phentolamine, yohimbine, or L-NMMA altered this response.

Conclusions— Nitric oxide seems to determine the absolute level of ATBF, whereas a major proportion of the postprandial enhancement of ATBF is under ß-adrenergic regulation in vivo in humans.

Key Words: blood flow • receptors, adrenergic, beta • nervous system, autonomic • nitric oxide synthase • insulin

This article has been cited by other articles:

				G. H. Goossens, S. E. McQuaid, A. L. Dennis, M. A. van Baak, E. E. Blaak, K. N. Frayn, W. H. M. Saris, and F. Karpe Angiotensin II: a major regulator of subcutaneous adipose tissue blood flow in humans J. Physiol., March 1, 2006; 571(2): 451 - 460. [Abstract] [Full Text] [PDF]

				J. S. Nicholas, S. J. D'Agostino, and S. J. Patel Arterial Compression of the Retro-Olivary Sulcus of the Ventrolateral Medulla in Essential Hypertension and Diabetes Hypertension, October 1, 2005; 46(4): 982 - 985. [Abstract] [Full Text] [PDF]

				F. Karpe, B. A. Fielding, S. W. Coppack, V. J. Lawrence, I. A. Macdonald, and K. N. Frayn Oscillations of Fatty Acid and Glycerol Release From Human Subcutaneous Adipose Tissue In Vivo Diabetes, May 1, 2005; 54(5): 1297 - 1303. [Abstract] [Full Text] [PDF]

				A. F. Dominiczak, D. Graham, M. W. McBride, N. J.R. Brain, W. K. Lee, F. J. Charchar, M. Tomaszewski, C. Delles, and C. A. Hamilton Cardiovascular Genomics and Oxidative Stress Hypertension, April 1, 2005; 45(4): 636 - 642. [Abstract] [Full Text] [PDF]

				K. Tsuda, I. Nishio, J.-L. Ardilouze, B. A. Fielding, J. M. Curry, K. N. Frayn, and F. Karpe Role of Leptin in Regulating Nitric Oxide Production and Membrane Microviscosity * Response Circulation, June 8, 2004; 109(22): e316 - e316. [Full Text] [PDF]