Exp Mol Med.  2009 Aug;41(8):569-576. 10.3858/emm.2009.41.8.062.

Angiotensin II-induced aortic ring constriction is mediated by phosphatidylinositol 3-kinase/L-type calcium channel signaling pathway

Affiliations
  • 1MRC for Ischemic Tissue Regeneration and Medical Research Institute, Pusan National University School of Medicine, Yangsan 626-870, Korea. sunsik@pusan.ac.kr
  • 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.

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 (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 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.

Keyword

calcium; calcium channels, L-type; muscle contraction; muscle, smooth; 1-phosphatidylinositol 3-kinase

MeSH Terms

1-Phosphatidylinositol 3-Kinase/*metabolism/pharmacology
Angiotensin II/metabolism/*pharmacology
Animals
Aorta, Thoracic/*drug effects/physiology
Calcium Channels, L-Type/drug effects/*metabolism
Muscle Contraction/drug effects
Muscle, Smooth, Vascular/drug effects/enzymology
Rats
Rats, Sprague-Dawley
Signal Transduction/*drug effects
Specific Pathogen-Free Organisms
Vasoconstriction/*drug effects
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