Ca2+/Calmodulin-Dependent and -Independent Mechanisms are Involved in Angiotension II-induced Contraction of Rat Aortic Smooth Muscle

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Background: Angiotensin II (Ang II) appears to play important roles in the pathogenesis of hypertension. However, the mechanism by which Ang II induces vascular smooth muscle contraction is not fully understood. The phosphorylation of myosin light chain (MLC) is an essential trigger of the cascade that initiates of smooth muscle contraction. In this study, we investigated the role of MLC phosphorylation on Ang II-induced vascular smooth muscle contraction. Methods: Rat thoracic aortas were used as an experimental substrates. We measured isometric tension, myosin light chain phosphorylation, intracellular concentration, mitogen-activated protein kinase phosphorylation, and tyrosine phosphorylation. Results: 100 nM Ang II increased smooth muscle contraction transiently in rat thoracic aorta. Ang II also increased intracellular and 20 kDa MLC phosphorylation. Pretreatment with 10M verapamil and 30M abolished the contraction developed at 30 seconds by Ang II, whereas pretreatment with 10M verapamil and 30M abolished the contraction and the intracellular increase induced at 2 minutes by Ang II. Moreover, pretreatment of 10M verapamil, 30M and 1M thapsigargin abolished the contraction as well as intracellular M increase developed at 30 seconds and 2 minutes by Ang II. However, MLC phosphorylation was not affected. GF109203X attenuated Ang II-induced contraction more so than ML-7. 100 nM Ang II increased tyrosine phosphorylation of mitogen-activated protein kinase, 68 and 125 kDa proteins. The 125 kDa protein was confirmed as paxillin in primary vascular smooth muscle cell culture. Conclusions: Ang II-induced contraction involves -dependent and independent components, and -dependent contraction by Ang II is mediated by voltage-dependent channel. Moreover, protein kinase C and the mitogen-activated protein kinase activation pathway are involved in Ang II-induced contraction.