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Trophic action of sympathetic nerves reduces arterial smooth muscle Ca 2+ sensitivity during early post‐natal development in rats
Author(s) -
Puzdrova V. A.,
Kudryashova T. V.,
Gaynullina D. K.,
Mochalov S. V.,
Aalkjaer C.,
Nilsson H.,
Vorotnikov A. V.,
Schubert R.,
Tarasova O. S.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12331
Subject(s) - endocrinology , medicine , myosin light chain kinase , contraction (grammar) , rho associated protein kinase , methoxamine , biology , rhoa , denervation , muscle contraction , receptor , myosin , agonist , electrical impedance myography , vasoconstriction , kinase , microbiology and biotechnology , signal transduction , vasodilation
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 α 1 ‐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 ( MYPT 1) and h‐ caldesmon) and weaker expression of proteins regulating Ca 2+ ‐independent contraction (Rho kinase, extracellular‐regulated kinases ( ERK 1/2) 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 , MYPT 1 and h‐ caldesmon and more ERK 1/2 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.