Mechanisms of acetylcholine‐mediated vasodilatation in young and aged human skin

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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 μmACh at four intradermal microdialysis sites: control (C, Ringer solution), NO synthase inhibited (NOS‐I, 10 mm l‐NAME), cyclooxygenase inhibited (COX‐I, 10 mmketorolac) 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 (%CVCmax) (28 mmsodium nitroprusside + local heating to 43°C). Baseline %CVCmaxwas increased in the O at COX‐I sites (COX‐I 16 ± 1, NOS‐I + COX‐I 16 ± 2versusC 10 ± 1%CVCmax;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 %CVCmaxduring ACh infusion between age groups, and the response was unchanged by NOS‐I (O: NOS‐I 35 ± 5versusC 38 ± 5%CVCmax;P= 0.84) (Y: NOS‐I 41 ± 4versusC 39 ± 4%CVCmax;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%CVCmaxversusC;P< 0.001 both groups; NOS‐I + COX‐I O: 32 ± 3versusY: 29 ± 2%CVCmax;versusC;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.

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