The Role of Endothelin Receptors on Sensory Nerve Mediated Dilation in Postmenopausal Women

• Published in: The FASEB journal Vol. 36; no. S1
• Main Authors: Del Vecchio, Angelica R., Welti, Laura M., Kuczmarski, Andrew V., McGinty, Shane J., Wong, Brett J., Wenner, Megan M.
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01-05-2022
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.R4755

Rapid local heating of the skin elicits biphasic vasodilation. The initial peak in skin blood flow (SkBF) is mediated by sensory nerves (i.e., the axon reflex). Both endothelin (ETA and ETB) receptors are located on axon terminals on nociceptor fibers, and therefore may be involved in the sensory nerve mediated vasodilation. Although prior work shows a blunted axon reflex with aging, this has yet to be examined in women, and the role of ETA and ETB receptors in this initial sensory nerve‐mediated vasodilatory response remains unclear.
PURPOSE
We tested the hypothesis that the initial peak is blunted in postmenopausal women (POST) compared to young women (YW), and that blockade of ETA and ETB receptors would improve sensory nerve‐mediated dilation in POST.
METHODS
We retrospectively analyzed data in 25 healthy YW (27±10 yr) and 16 healthy POST (56±1 yr). Cutaneous vasodilation to local heating was measured using laser doppler flowmetry during microdialysis perfusions of lactated Ringer’s (control), ETA receptor blockade (BQ‐123, 500nM), and ETB receptor blockade (BQ‐788, 300nM). Cutaneous vascular conductance (CVC) was calculated as SkBF/MAP at baseline and during the initial peak of local heating (42°C); CVC were normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C.
RESULTS
All women were normotensive (MAP: YW 83±8 mmHg; POST 94±2 mmHg, p < 0.001) and not obese (YW 23±3 kg/m2; POST 24±1 kg/m2, p = 0.153). Sensory nerve‐mediated dilation at the control site was reduced in POST (YW 63 ±14 vs POST 49 ±17 %CVCmax, p=0.004). Blockade of ETA (YW 54 ±10 vs POST 55 ±9 %CVCmax, p=0.579) and ETB (YW 62 ±17 vs POST 59 ±13 %CVCmax, p=0.476) receptors did not impact the initial peak of local heating in either group.
CONCLUSIONS
These preliminary data suggest the sensory nerve‐mediated vasodilation during local heating is attenuated with aging in women, but endothelin receptors do not contribute to this age‐related decrease. Additional research is needed to further understand the interactions between sex hormones and aging in regulating sensory nerve mediated vasodilation.