Trophic sympathetic influence weakens pro-contractile role of Cl- channels in rat arteries during postnatal maturation

Sci Rep. 2020 Nov 17;10(1):20002. doi: 10.1038/s41598-020-77092-0.

Abstract

Membrane transporters and their functional contribution in vasculature change during early postnatal development. Here we tested the hypothesis that the contribution of Cl- channels to arterial contraction declines during early postnatal development and this decline is associated with the trophic sympathetic influence. Endothelium-denuded saphenous arteries from 1- to 2-week-old and 2- to 3-month-old male rats were used. Arterial contraction was assessed in the isometric myograph, in some experiments combined with measurements of membrane potential. mRNA and protein levels were determined by qPCR and Western blot. Sympathectomy was performed by treatment with guanethidine from the first postnatal day until 8-9-week age. Cl- substitution in the solution as well as Cl--channel blockers (MONNA, DIDS) had larger suppressive effect on the methoxamine-induced arterial contraction and methoxamine-induced depolarization of smooth muscle cells in 1- to 2-week-old compared to 2- to 3-month-old rats. Vasculature of younger group demonstrated elevated expression levels of TMEM16A and bestrophin 3. Chronic sympathectomy increased Cl- contribution to arterial contraction in 2-month-old rats that was associated with an increased TMEM16A expression level. Our study demonstrates that contribution of Cl- channels to agonist-induced arterial contraction and depolarization decreases during postnatal development. This postnatal decline is associated with sympathetic nerves development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anoctamin-1 / metabolism
  • Arteries / drug effects
  • Arteries / metabolism*
  • Chloride Channels / metabolism*
  • Male
  • Methoxamine / pharmacology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / physiology
  • Rats
  • Rats, Wistar
  • Sympathectomy / methods
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / metabolism*
  • Sympathetic Nervous System / physiology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology

Substances

  • Anoctamin-1
  • Chloride Channels
  • Methoxamine