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

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...

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Bibliographic Details
Published in:Acta physiologica (Oxford, England) England), 2014-10, Vol.212 (2), p.128-141
Main Authors: Puzdrova, V A, Kudryashova, T V, Gaynullina, D K, Mochalov, S V, Aalkjaer, C, Nilsson, H, Vorotnikov, A V, Schubert, R, Tarasova, O S
Format: Article
Language:English
Subjects:
Adrenergic Fibers - physiology
Animals
Arteries - growth & development
Blotting, Western
Calcium - metabolism
Male
Muscle Contraction - physiology
Muscle, Smooth, Vascular - metabolism
Rats
Rats, Wistar
Sympathectomy
Vascular Remodeling - physiology
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Summary: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. 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. 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. 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.
ISSN:1748-1716
DOI:10.1111/apha.12331