Angiotensin II-induced aortic ring constriction is mediated by phosphatidylinositol 3-kinase/L-type calcium channel signaling pathway.
10.3858/emm.2009.41.8.062
- Author:
Kee Hun DO
1
;
Min Sung KIM
;
Jae Ho KIM
;
Byung Yong RHIM
;
Won Suk LEE
;
Chi Dae KIM
;
Sun Sik BAE
Author Information
1. MRC for Ischemic Tissue Regeneration and Medical Research Institute, Pusan National University School of Medicine, Yangsan 626-870, Korea. sunsik@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
calcium;
calcium channels, L-type;
muscle contraction;
muscle, smooth;
1-phosphatidylinositol 3-kinase
- MeSH:
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
- From:Experimental & Molecular Medicine
2009;41(8):569-576
- CountryRepublic of Korea
- Language:English
-
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.
