The Impact of ET B Receptors on the Axon Reflex During Local Heating in Healthy Young Women

Abstract

Endothelin-1 (ET-1) is a vasoconstrictor that acts on the vasculature through ETA and ETB receptors. Both ETA and ETB receptors are located in the skin and are involved in regulating skin blood flow. ETB receptors are also located on axon terminals on c-type nociceptor fibers. Rapid local heating stimulates the axon reflex which has been established as a mediator of the initial vasodilation response. Although ETA receptors have been shown to augment the axon reflex resulting in a vasodilation, less is known about the role of the ETB receptors on the axon reflex. Purpose The purpose of this study was to determine the contribution of ETB receptors to the axon reflex response. Methods We retrospectively analyzed data in 24 healthy young women (27±10 yrs). Cutaneous vasodilatory responses to local heating were measured using laser doppler flowmetry during microdialysis perfusions of lactated Ringer's (control) and ETB receptor blockade (BQ-788, 300nM). Cutaneous vascular conductance (CVC) was calculated during the initial peak and nadir of the axon reflex during local heating (42°C), and normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C. We used paired samples t-tests to analyze differences in vasodilation between control and ETB receptor blockade sites. Results All subjects were normotensive (MAP: 83±8 mmHg) and had a normal BMI (23±3 kg/m2). There were no significant differences in skin blood flow between control and ETB receptor blockade sites during initial peak (control: 63 ±15; ETB receptor blockade: 62±17 %CVC max, P=0.70) or nadir (control: 52±16; ETB receptor blockade: 50±18 %CVC max, P=0.49). There was also no significant difference between conditions in time to initial peak (control: 142±75; ETB receptor blockade: 140±53 s, P=0.79). Conclusions These preliminary findings suggest ETB receptors do not impact axon reflex mediated vasodilation during local heating in healthy young women. Future research is needed to understand the mechanisms contributing to the axon reflex to regulate blood flow in the cutaneous circulation.