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

被引:196
作者
Holowatz, LA
Thompson, CS
Minson, CT
Kenney, WL
机构
[1] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA
[2] Penn State Univ, Physiol Program, University Pk, PA 16802 USA
[3] Univ Oregon, Dept Human Physiol, Eugene, OR 97401 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2005年 / 563卷 / 03期
关键词
D O I
10.1113/jphysiol.2004.080952
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 (0: 69 I years) subjects underwent infusions of 137.5 mu m 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 (%CVCmax) (28 mM sodium nitroprusside + local heating to 43 degrees C). Baseline %CVCmax was increased in the 0 at COX-I sites (COX-I 16 1, NOS-I + COX-I 16 +/- 2 versus C 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 %CVCmax during ACh infusion between age groups, and the response was unchanged by NOS-I (O: NOS-I 35 +/- 5 versus C 38 +/- 5%CVCmax; P = 0.84) (Y: NOS-I 41 +/- 4 versus C 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%CVCmax versus C; P < 0.001 both groups; NOS-I + COX-I O: 32 +/- 3 versus Y: 29 +/- 2%CVCmax; 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.
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收藏
页码:965 / 973
页数:9
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