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The Inhibitory Effect of Pioglitazone on Agonist-dependent Vascular Contractility  

Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
Cha, Sung-Jae (Department of Surgery, College of Medicine, Chung-Ang University)
Jeong, Ji-Hoon (Department of Pharmacology, College of Medicine, Chung-Ang University)
Publication Information
Molecular & Cellular Toxicology / v.4, no.1, 2008 , pp. 72-77 More about this Journal
Abstract
The present study was undertaken to determine whether pioglitazone treatment influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Pioglitazone decreased Rho-kinase activating agonist-induced contraction but not phorbol ester-induced contraction suggesting the least involvement of $Ca^{2+}$-independent thin filament regulation of contractility. Furthermore, pioglitazone decreased thromboxane $A_2$ mimeticinduced phosphorylation of MYPT1 at Thr855, the newly-highlighted site, instead of Thr696. In conclusion, this study provides the evidence and possible related mechanism concerning the vasorelaxing effect of pioglitazone as an antihypertensive on the agonist-induced contraction in rat aortic rings regardless of endothelial function.
Keywords
MYPT1; Phorbol ester; Pioglitazone; Rhokinase; Thromboxane $A_2$ mimetic;
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1 Waugh, J. et al. Pioglitazone: a review of its type 2 diabetes mellitus. Drugs 66:85-109 (2006)   DOI
2 Leung, T., Manser, E., Tan, L. & Lim, L. A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J Biol Chem 270:29051-29054 (1995)   DOI
3 Tack, C. J. & Smits, P. Thiazolidinedione derivatives in type 2 diabetes mellitus. Neth J Med 64:166-174 (2006)
4 Matsui, T. et al. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J 15:2208-2216 (1996)
5 Wilson, D. P. et al. Thromboxane $A_2$-induced contraction of rat caudal arterial smooth muscle involves activation of $Ca^{2+}$ entry and $Ca^{2+}$ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem J 389:763-774 (2005)   DOI   ScienceOn
6 Yki-Jarvinen, H. Thiazolidinediones. N Engl J Med 351:1106-1118 (2004)   DOI   ScienceOn
7 Marx, N. et al. Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 83:1097-1103 (1998)   DOI   ScienceOn
8 Gerthoffer, W. T. et al. Activation of MAP kinases and phosphorylation of caldesmon in canine colonic smooth muscle. J Physiol 495:597-609 (1996)   DOI
9 Somlyo, A. P. & Somlyo, A. V. From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta Physiol Scand 164:437-448 (1998)   DOI   ScienceOn
10 Uemura, S. et al. Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress. Circ Res 88:1291-1298 (2001)   DOI   ScienceOn
11 Somlyo, A. P. & Somlyo, A. V. Signal transduction and regulation in smooth muscle. Nature 372:231-236 (1994)   DOI   ScienceOn
12 Uehata, M. et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389:990-994 (1997)   DOI   ScienceOn
13 Wier, W. G. & Morgan, K. G. $\alpha$1-Adrenergic signaling mechanisms in contraction of resistance arteries. Rev Physiol Biochem Pharmacol 150:91-139 (2003)
14 Senses, V. et al. Effect of 5-aminoimidazole-4-carboxamide riboside (AICA-r) on isolated thoracic aorta responses in streptozotocin-diabetic rats. J Basic Clin Physiol Pharmacol 12:227-248 (2001)
15 Marx, N. et al. PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease. Arterioscler Thromb Vasc Biol 19:546-551 (1999)   DOI   ScienceOn
16 Kitazawa, T., Masuo, M. & Somlyo, A. P. Proteinmediated inhibition of myosin light-chain phospha-tase in vascular smooth muscle. Proc Natl Acad Sci USA 88:9307-9310 (1991)
17 Wooldridge, A. A. et al. Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J Biol Chem 279:34496-34504 (2004)   DOI   ScienceOn
18 Sakurada, S. et al. $Ca^{2+}$-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ Res 93:548-556 (2003)   DOI   ScienceOn
19 Gohla, A., Schultz, G. & Offermanns, S. Roles for G(12)/G(13) in agonist-induced vascular smooth muscle cell contraction. Circ Res 87:221-227 (2000)   DOI   ScienceOn
20 Majithiya, J. B., Paramar, A. N. & Balaraman, P. R. Pioglitazone, a PPARgamma agonist, restores endothelial function in aorta of streptozotocin-induced diabetic rats. Cardiovasc Res 66:150-161 (2005)   DOI   ScienceOn
21 Tsai, M. H. & Jiang, M. J. Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle contraction. Pflugers Arch 453:223-232 (2006)   DOI
22 Giles, T. D. & Sander, A. G. Effect of thiazolidinediones on blood pressure. Curr Hypertens Rep 9:332-337 (2007)   DOI   ScienceOn