title: Mechanisms of acetylcholine-mediated vasodilatation in young and aged human skin.
abstract: Thermoregulatory cutaneous vasodilatation (VD) is attenuated in aged skin. While acetylcholine (ACh) plays a role in thermally mediated VD, the precise mechanisms through which ACh-mediated VD acts and whether those downstream mechanisms change with ageing are unclear. We tested the hypotheses that both nitric oxide (NO)- and prostanoid-mediated pathways contribute to exogenous ACh-mediated VD, and that both are attenuated with advanced age. Twelve young (Y: 23 +/- 1 years) and 10 older (O: 69 +/- 1 years) subjects underwent infusions of 137.5 mum ACh at four intradermal microdialysis sites: control (C, Ringer solution), NO synthase inhibited (NOS-I, 10 mm l-NAME), cyclooxygenase inhibited (COX-I, 10 mm ketorolac) and NOS-I + COX-I. Red blood cell flux was monitored using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated (laser-Doppler flux/mean arterial pressure) and normalized to maximal CVC (%CVC(max)) (28 mm sodium nitroprusside + local heating to 43 degrees C). Baseline %CVC(max) was increased in the O at COX-I sites (COX-I 16 +/- 1, NOS-I + COX-I 16 +/- 2 versus C 10 +/- 1%CVC(max); P < 0.001) but not in the young, suggesting an age-related shift toward COX vasoconstrictors contributing to basal cutaneous vasomotor tone. There was no difference in peak %CVC(max) during ACh infusion between age groups, and the response was unchanged by NOS-I (O: NOS-I 35 +/- 5 versus C 38 +/- 5%CVC(max); P = 0.84) (Y: NOS-I 41 +/- 4 versus C 39 +/- 4%CVC(max); P = 0.67). COX-I and NOS-I + COX-I attenuated the peak CVC response to ACh in both groups (COX-I O: 29 +/- 3, Y: 22 +/- 2%CVC(max) versus C; P < 0.001 both groups; NOS-I + COX-I O: 32 +/- 3 versus Y: 29 +/- 2%CVC(max); versus C; P < 0.001 both groups). ACh mediates cutaneous VD through prostanoid and non-NO-, non-prostanoid-dependent pathways. Further, older subjects have a diminished prostanoid contribution to ACh-mediated VD.
authors.affiliation: The Pennsylvania State University, Noll Laboratory, University Park, PA 16802, USA. lma191@psu.edu
authors.forename: Lacy A
authors.initials: LA
authors.lastname: Holowatz
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: Thompson
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Minson
authors.forename: W Larry
authors.initials: WL
authors.lastname: Kenney
mesh_terms: D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D001783:Blood Flow Velocity; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D012879:Skin Physiological Phenomena; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D011453:Prostaglandins; D009569:Nitric Oxide; D000109:Acetylcholine