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

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

扫码查看
原文链接
  • NSTL
  • Wiley
New Findings What is the central question of this study? Do transmembrane member 16A (TMEM16A) blockers modulate the activation of heat loss responses of sweating and cutaneous vasodilatation? What are the main finding and its importance? Relative to the vehicle control site, TMEM16A blockers T16Ainh‐A01 and benzbromarone had no effect on sweat rate or cutaneous vascular conductance during whole‐body heating inducing a 1.1?±?0.1°C increase in core temperature above baseline resting levels. These results suggest that TMEM16A blockers T16Ainh‐A01 and benzbromarone do not modulate the regulation of sweating and cutaneous vasodilatation during whole‐body heat stress. Abstract Animal and in vitro studies suggest that transmembrane member 16A (TMEM16A), a Ca2+‐activated Cl? channel, contributes to regulating eccrine sweating. However, direct evidence supporting this possibility in humans is lacking. We assessed the hypothesis that TMEM16A blockers attenuate sweating during whole‐body heating in humans. Additionally, we assessed the associated changes in the heat loss response of cutaneous vasodilatation to determine if a functional role of TMEM16A may exist. Twelve young (24?±?2?years) adults (six females) underwent whole‐body heating using a water‐perfused suit to raise core temperature 1.1?±?0.1°C above baseline. Sweat rate and cutaneous vascular conductance (normalized to maximal conductance via administration of sodium nitroprusside) were evaluated continuously at four forearm skin sites treated continuously by intradermal microdialysis with (1) lactated Ringer's solution (control), (2) 5% dimethyl sulfoxide (DMSO) serving as a vehicle control, or (3) TMEM16A blockers 1?mM T16Ainh‐A01 or 2?mM benzbromarone dissolved in 5% DMSO solution. All drugs were administered continuously via intradermal microdialysis. Whole‐body heating increased core temperature progressively and this was paralleled by an increase in sweat rate and cutaneous vascular conductance at all skin sites. However, sweat rate (all P?>?0.318) and cutaneous vascular conductance (all P?≥?0.073) did not differ between the vehicle control site relative to the TMEM16A blocker‐treated sites. Collectively, our findings indicate that TMEM16A blockers T16Ainh‐A01 and benzbromarone do not modulate the regulation of sweating and cutaneous vasodilatation during whole‐body heating in young adults in vivo.

CaCCheat strokehyperthermiathermoregulation

Naoto Fujii、Tatsuro Amano、Glen P. Kenny、Toby Mündel、Tze‐Huan Lei、Yasushi Honda、Narihiko Kondo、Takeshi Nishiyasu

展开 >

Faculty of Health and Sport Sciences,University of Tsukuba

Laboratory for Exercise and Environmental Physiology,Niigata University

Human and Environmental Physiology Research Unit,University of Ottawa

School of Sport Exercise and Nutrition,Massey University

College of Physical Education,Hubei Normal University

Laboratory for Applied Human Physiology,Kobe University

展开 >

2022

10.1113/EP090521

Experimental physiology.

Experimental physiology.

ISSN：0958-0670
年,卷(期)：2022.107(8)
  • 1
  • 48