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Article
Impaired Endothelium-dependent Vasodilation in Overweight and Obese Adult Humans is Not Limited to Muscarinic Receptor Agonists
American Journal of Physiology, Heart and Circulatory Physiology
  • Gary P. Van Guilder
  • Brian L Stauffer
  • Jared J Greiner
  • Christopher A Desouza
Document Type
Article
Publication Date
4-1-2008
Abstract
Muscarinic receptor agonists have primarily been used to characterize endothelium-dependent vasodilator dysfunction with overweight/obesity. Reliance on a single class of agonist, however, yields limited, and potentially misleading, information regarding endothelial vasodilator capacity. The aims of this study were to determine 1) whether the overweight/obesity-related reduction in endothelium-dependent vasodilation extends beyond muscarinic receptor agonists and 2) whether the contribution of nitric oxide (NO) to endothelium-dependent vasodilation is reduced in overweight/obese adults. Eighty-six middle-aged and older adults were studied: 42 normal-weight (54 +/- 1 yr, 21 men and 21 women, body mass index = 23.4 +/- 0.3 kg/m(2)) and 44 overweight/obese (54 +/- 1 yr, 28 men and 16 women, body mass index = 30.3 +/- 0.6 kg/m(2)) subjects. Forearm blood flow (FBF) responses to intra-arterial infusions of acetylcholine in the absence and presence of the endothelial NO synthase inhibitor N(G)-monomethyl-l-arginine, methacholine, bradykinin, substance P, isoproterenol, and sodium nitroprusside were measured by strain-gauge plethysmography. FBF responses to each endothelial agonist were significantly blunted in the overweight/obese adults. Total FBF (area under the curve) to acetylcholine (50 +/- 5 vs. 79 +/- 4 ml/100 ml tissue), methacholine (55 +/- 4 vs. 86 +/- 5 ml/100 ml tissue), bradykinin (62 +/- 5 vs. 85 +/- 4 ml/100 ml tissue), substance P (37 +/- 4 vs. 57 +/- 5 ml/100 ml tissue), and isoproterenol (62 +/- 4 vs. 82 +/- 6 ml/100 ml tissue) were 30%-40% lower in the overweight/obese than normal-weight adults. N(G)-monomethyl-l-arginine significantly reduced the FBF response to acetylcholine to the same extent in both groups. There were no differences between the groups in the FBF responses to sodium nitroprusside. These results indicate that agonist-stimulated endothelium-dependent vasodilation is universally impaired with overweight/obesity. Moreover, this impairment appears to be independent of NO.
Pages
18
Type
text
Format
application/pdf
Language
en
PMCID
18281379
DOI of Published Version
10.1152/ajpheart.01281.2007
Publisher
American Physiological Society
Rights

In Copyright - Non-Commercial Use Permitted
http://rightsstatements.org/vocab/InC-NC/1.0/

Comments

This is the NIH Public Access Author Manuscript. The Version of Record was published in Am J Physiol Heart Circ Physiol. 2008 April ; 294(4): H1685–H1692. doi:10.1152/ajpheart.01281.2007.

Citation Information
Gary P. Van Guilder, Brian L Stauffer, Jared J Greiner and Christopher A Desouza. "Impaired Endothelium-dependent Vasodilation in Overweight and Obese Adult Humans is Not Limited to Muscarinic Receptor Agonists" American Journal of Physiology, Heart and Circulatory Physiology Vol. 294 Iss. 4 (2008) p. 1685 - 1692
Available at: http://works.bepress.com/gary-vanguilder/16/