ET_B receptor-mediated vasodilation is regulated by estradiol in young women

Abstract

The endothelin-B (ETB) receptor mediates vasodilation in young women, an effect lost following menopause. It is unclear whether these alterations are due to aging or changes in estradiol (E2). During endogenous hormone suppression (GnRH antagonist), blockade of ETB receptors enhanced cutaneous microvascular vasodilation. However, during E2 administration, blockade of ETB receptors attenuated vasodilation, indicating that the ETB receptor mediates dilation in the presence of E2. In young women, ETB receptors mediate vasodilation in the presence of E2, an effect that is lost when E2 is suppressed.

Endothelin A receptor inhibition increases nitric oxide-dependent vasodilation independent of superoxide in non-Hispanic Black young adults

“…Previous data also suggest an influence of sex hormones on ET-1 receptor-mediated responses in women ( 45 , 46 , 48 , 49 , 54 ), and ET A R antagonism appears to improve cutaneous microvascular endothelium-dependent and NO-dependent vasodilation in both young Black and White women ( 35 ). Furthermore, there appear to be mechanistic differences in the regulation of vascular function between non-Hispanic Black men and women ( 9 , 68 ).…”

“…As such, the present data support a mechanism for ET A R in blunted vasodilator responses in young, normotensive non-Hispanic Black adults. However, as this study was designed to antagonize the ET A R receptor, and not to decrease ET-1 itself, it is possible that ET A R antagonism allowed greater ET-1 signaling through endothelial ET B R, which mediates vasodilation and serves as an ET-1 clearance mechanism ( 45 , 46 , 49 ). In this subset of participants, ET A R appeared to have a greater effect on NO mechanisms.…”

“…The second phase is a sustained plateau mediated largely (∼60%–80%) by endothelial NO-dependent mechanisms with contributions from other pathways, including endothelial-derived hyperpolarizing factors (EDHFs), adenosine receptors, and histamine receptors ( 37 , 40 – 44 ). The ET A R subtype is functional in human skin and has been effectively inhibited during local heating ( 35 , 45 – 49 ). Considering that cutaneous microvascular function can be used as a surrogate of systemic microvascular function ( 50 ), the present in vivo assessment of cutaneous microvascular vasodilation yields important context of the influence of ET-1 binding to the ET A R subtype and possible subsequent superoxide generation on vascular function in young, healthy non-Hispanic Black and non-Hispanic White adults.…”

Serum, interstitial and sweat ATP in humans exposed to heat stress: Insights into roles of ATP in the heat loss responses

“…Female participants were tested during their self‐reported early follicular phase of their menstruation (within 6 days from the initiation of menstruation) when female sex hormone concentrations are at their lowest concentrations. Limiting our assessment of females during the early follicular phase allowed us to minimize the influence of female sex hormones on the activation of cutaneous vasodilation (Brunt et al, 2011; Fujii et al, 2020; Shoemaker et al, 2021) and sweating (Gagnon et al, 2013; Inoue et al, 2014; Okamoto & Amano, 2021). Participants were not permitted to consume alcohol and caffeine for >12 h, and any food for 2 h before the experiments.…”

TMEM16A blockers T16Ainh‐A01 and benzbromarone do not modulate the regulation of sweating and cutaneous vasodilatation in humans in vivo

“…Young females were tested ≤6 days from the beginning of menstruation wherein levels of female sex hormones appear to be low. This was necessary to minimize the established influence that elevations in sex hormone can modulate the regulation of sweating (Okamoto & Amano, 2021) and cutaneous vascular responses (Shoemaker et al., 2021) in females. No young females used contraceptives.…”