Institut for Biomedicin

Christian Aalkjær

Trophic action of sympathetic nerves reduces arterial smooth muscle Ca(2+) sensitivity during early post-natal development in rats

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • V A Puzdrova
  • ,
  • T V Kudryashova, Danmark
  • D K Gaynullina, Danmark
  • S V Mochalov, Danmark
  • C Aalkjaer
  • H Nilsson
  • ,
  • A V Vorotnikov, Danmark
  • R Schubert
  • ,
  • O S Tarasova

AIM: A decrease in the Ca(2+) sensitivity of smooth muscle contraction is a hallmark of functional remodelling of blood vessels during development. However, the responsible factors are largely unknown. Here, we tested the hypothesis that the post-natal decline of arterial Ca(2+) sensitivity is the result of trophic effects of sympathetic nerves.

METHODS: Contractile responses, intracellular Ca(2+) levels and protein expression profiles were compared in saphenous arteries from young (1- and 2-week-old) and adult rats using wire myography, Ca(2+) fluorimetry and Western blotting respectively.

RESULTS: We observed a lower Ca(2+) sensitivity of contractions induced by methoxamine, an agonist of α1 -adrenoceptors, and U46619, an agonist of thromboxane A2 receptors, in arteries from adult as compared to young animals. Post-natal maturation was associated with stronger expression of regulatory proteins mediating Ca(2+) -dependent contraction (myosin light chain kinase (MLCK), myosin targeting subunit (MYPT1) and h-caldesmon) and weaker expression of proteins regulating Ca(2+) -independent contraction (Rho kinase, extracellular-regulated kinases (ERK1/2) and mitogen-activated protein kinases p38 MAPK) in vessels from adult rats. To eliminate the trophic action of sympathetic nerves, we performed lumbar sympathectomy in adult rats. This resulted in higher Ca(2+) sensitivity of agonist-induced contractions in denervated as compared to control arteries. Furthermore, denervated arteries contained less MLCK, MYPT1 and h-caldesmon and more ERK1/2 and p38 MAPK.

CONCLUSIONS: Sympathetic denervation reverses developmental changes both in Ca(2+) sensitivity and in the expression of regulatory proteins back to the early post-natal phenotype in the rat saphenous artery. We conclude that trophic effects of sympathetic nerves govern functional remodelling of arteries during early post-natal development.

OriginalsprogEngelsk
TidsskriftActa Physiologica (Online)
Vol/bind212
Nummer2
Sider (fra-til)128-41
Antal sider14
ISSN1748-1716
DOI
StatusUdgivet - okt. 2014

    Forskningsområder

  • Adrenergic Fibers, Animals, Arteries, Blotting, Western, Calcium, Male, Muscle Contraction, Muscle, Smooth, Vascular, Rats, Rats, Wistar, Sympathectomy, Vascular Remodeling

Se relationer på Aarhus Universitet Citationsformater

ID: 90612777