title: Evidence for agonist-specific endothelial vasodilator dysfunction with ageing in healthy humans.
abstract: Endothelium-dependent vasodilatation declines with advancing age in humans independently of disease. The mechanisms responsible for this decline are not clear. We determined whether the age-related reduction in endothelium-dependent vasodilatation in response to acetylcholine reflects a specific agonist-related defect or rather a more general endothelial cell vasomotor abnormality. Twenty-two young (23-35 years) and 41 older (50-76 years) healthy men were studied. Forearm blood flow (FBF) responses to intra-arterial infusions of acetylcholine, bradykinin, substance P, isoproterenol (isoprenaline) and sodium nitroprusside were measured by strain-gauge plethysmography. There were no differences in resting FBF between the young (3.9 +/- 0.2 ml (100 ml tissue)(-1) x min(-1)) and older men (4.0 +/- 0.2 ml (100 ml tissue)(-1) x min(-1)). The increase in FBF at the highest dose of acetylcholine was approximately 30 % lower (P < 0.01) in the older (from 4.0 +/- 0.2 to 12.3 +/- 0.7 ml (100 ml tissue)(-1) x min(-1)) compared with young men (from 3.9 +/- 0.2 to 17.1 +/- 1.5 ml (100 ml tissue)(-1) x min(-1)). In contrast to acetylcholine, the FBF responses to the other endothelial agonists were not impaired with age. The maximum increases in FBF in response to bradykinin (19.2 +/- 1.0 vs. 20.2 +/- 0.9 ml (100 ml tissue)(-1) x min(-1)), substance P (15.1 +/- 0.8 vs. 16.8 +/- 0.7 ml (100 ml tissue)(-1) x min(-1)) and isoproterenol (17.5 +/- 0.9 vs. 17.5 +/- 0.9 ml (100 ml tissue)(-1) x min(-1)) were not significantly different between the older and young subjects. There were no age-related differences in the FBF responses to sodium nitroprusside. These results demonstrate that, although acetylcholine-induced vasodilatation is impaired with age, forearm endothelial vasodilatation in response to bradykinin, substance P and isoproterenol are well preserved in healthy men. Moreover, these findings suggest that agonist-stimulated endothelium-dependent vasodilatation is not universally impaired with age.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Kinesiology and Applied Physiology, University of Colorado, Boulder, CO 80309, USA. desousa@colorado.edu
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Clevenger
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Derek T
authors.initials: DT
authors.lastname: Smith
authors.forename: Greta L
authors.initials: GL
authors.lastname: Hoetzer
authors.forename: Linda F
authors.initials: LF
authors.lastname: Shapiro
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D014665:Vasodilator Agents; D009599:Nitroprusside; D013373:Substance P; D007545:Isoproterenol; D000109:Acetylcholine; D001920:Bradykinin