Puzdrova V A, Kudryashova T V, Gaynullina D K, Mochalov S V, Aalkjaer C, Nilsson H, Vorotnikov A V, Schubert R, Tarasova O S
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.
Acta Physiol (Oxf). 2014 Oct;212(2):128-41. doi: 10.1111/apha.12331. Epub 2014 Jul 3.
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.
平滑肌收缩的钙（Ca2+）敏感性降低是血管在发育过程中功能重塑的一个标志。然而，其相关因素在很大程度上尚不清楚。在此，我们检验了一个假说，即出生后动脉钙敏感性的下降是交感神经营养作用的结果。
分别使用线肌动描记法、钙荧光测定法和蛋白质免疫印迹法，比较了幼年（1周龄和2周龄）和成年大鼠隐动脉的收缩反应、细胞内钙水平和蛋白质表达谱。
我们观察到，与幼年动物相比，成年动物动脉中由α1 -肾上腺素能受体激动剂甲氧明和血栓素A2受体激动剂U46619诱导的收缩的钙敏感性较低。出生后成熟与介导钙依赖性收缩的调节蛋白（肌球蛋白轻链激酶（MLCK）、肌球蛋白靶向亚基（MYPT1）和h -钙调蛋白）的更强表达以及成年大鼠血管中调节非钙依赖性收缩的蛋白（Rho激酶、细胞外调节激酶（ERK1/2）和丝裂原活化蛋白激酶p38 MAPK）的较弱表达相关。为消除交感神经的营养作用，我们对成年大鼠进行了腰交感神经切除术。这导致去神经支配的动脉与对照动脉相比，激动剂诱导的收缩的钙敏感性更高。此外，去神经支配的动脉中MLCK、MYPT1和h -钙调蛋白含量较少，而ERK1/2和p38 MAPK含量较多。
交感神经去支配使大鼠隐动脉中钙敏感性和调节蛋白表达的发育变化逆转回出生后早期表型。我们得出结论，交感神经的营养作用在出生后早期发育过程中支配动脉的功能重塑。
