Angiotensin II-induced aortic ring constriction is mediated by phosphatidylinositol 3-kinase/L-type calcium channel signaling pathway |
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Authors: | Kee Hun Do Min Sung Kim Jae Ho Kim Byung-Yong Rhim Won Suk Lee Chi Dae Kim and Sun Sik Bae |
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Institution: | 1MRC for Ischemic Tissue Regeneration and Medical Research Institute, Pusan National University School of Medicine, Yangsan 626-870, Korea.;2Department of Pharmacology, Pusan National University School of Medicine, Yangsan 626-870, Korea.;3Department of Physiology, Pusan National University School of Medicine, Yangsan 626-870, Korea. |
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Abstract: | Angiotensin II (AngII) is a crucial hormone that affects vasoconstriction and exerts hypertrophic effects on vascular smooth muscle cells. Here, we showed that phosphatidylinositol 3-kinase-dependent calcium mobilization plays pivotal roles in AngII-induced vascular constriction. Stimulation of rat aortic vascular smooth muscle cell (RASMC)-embedded collagen gel with AngII rapidly induced contraction. AngII-induced collagen gel contraction was blocked by pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor ({"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002) whereas ERK inhibitor (PD98059) was not effective. AngII-induced collagen gel contraction was significantly blocked by extracellular calcium depletion by EGTA or by nifedipine which is an L-type calcium channel blocker. In addition, AngII-induced calcium mobilization was also blocked by nifedipine and EGTA, whereas intracellular calcium store-depletion by thapsigargin was not effective. Finally, pretreatment of rat aortic ring with {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and nifedipine significantly reduced AngII-induced constriction. Given these results, we suggest that PI3K-dependent activation of L-type calcium channels might be involved in AngII-induced vascular constriction. |
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Keywords: | calcium calcium channels L-type muscle contraction muscle smooth 1-phosphatidylinositol 3-kinase |
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