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Mechanisms of acetylcholine‐mediated vasodilatation in young and aged human skin
Author(s) -
Holowatz Lacy A.,
Thompson Caitlin S.,
Minson Christopher T.,
Kenney W. Larry
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.080952
Subject(s) - microdialysis , sodium nitroprusside , acetylcholine , vasodilation , nitric oxide , medicine , chemistry , nitric oxide synthase , endocrinology , prostanoid , anesthesia , prostaglandin , central nervous system
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 μ m ACh at four intradermal microdialysis sites: control (C, Ringer solution), NO synthase inhibited (NOS‐I, 10 m m l ‐NAME), cyclooxygenase inhibited (COX‐I, 10 m m 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 m m sodium nitroprusside + local heating to 43°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.