title: Trophic action of sympathetic nerves reduces arterial smooth muscle Ca(2+) sensitivity during early post-natal development in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia; Centre for Biomedicine and Medical Technology Mannheim (CBTM), Research Division Cardiovascular Physiology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: V A
authors.initials: VA
authors.lastname: Puzdrova
authors.forename: T V
authors.initials: TV
authors.lastname: Kudryashova
authors.forename: D K
authors.initials: DK
authors.lastname: Gaynullina
authors.forename: S V
authors.initials: SV
authors.lastname: Mochalov
authors.forename: C
authors.initials: C
authors.lastname: Aalkjaer
authors.forename: H
authors.initials: H
authors.lastname: Nilsson
authors.forename: A V
authors.initials: AV
authors.lastname: Vorotnikov
authors.forename: R
authors.initials: R
authors.lastname: Schubert
authors.forename: O S
authors.initials: OS
authors.lastname: Tarasova
mesh_terms: D000320:Adrenergic Fibers / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000254:growth & development*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013562:Sympathectomy; D066253:Vascular Remodeling / Q000502:physiology*
chemical_list: D002118:Calcium
keywords: denervation; development; protein expression; rat; saphenous artery; sympathetic nervous system