title: Impaired endothelium-dependent vasodilation in overweight and obese adult humans is not limited to muscarinic receptor agonists.
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.
authors.affiliation: Dept. of Integrative Physiology, Univ. of Colorado, 354 UCB, Boulder, CO 80309. desouzac@colorado.edu).
authors.forename: Gary P
authors.initials: GP
authors.lastname: Van Guilder
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Desouza
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001920:Bradykinin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000008:administration & dosage*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000008:administration & dosage; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D014665:Vasodilator Agents; D016210:Methacholine Chloride; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester