17 β -estradiol induces vasorelaxation in a g protein-coupled receptor 30-independent manner

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Reference Figure. 17 β -Estradiol induces vasorelaxation in a G protein-coupled receptor 30-independent manner Young Mi Seok 1 , Eun Jin Jang 2 , Oliver Reiser 3 , Markus Hager 3 , and In Kyeom Kim 1,2,4 * - PowerPoint PPT Presentation

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17-Estradiol induces vasorelaxation in a G protein-coupled receptor 30-independent manner Young Mi Seok1, Eun Jin Jang2, Oliver Reiser3, Markus Hager3, and In Kyeom Kim1,2,4*1Cardiovascular Research Institute, 2Department of Pharmacology, 4Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea; 3Organic Chemistry institute, University of Regensburg, Universittsstr.31, Regensburg, Germany *Correspondence and Proofs In Kyeom Kim, M.D., Ph.D.Department of PharmacologyKyungpook National University School of Medicine101 Dongin-2-GaDaegu, 700-422, Republic of KoreaTel: +82-53-420-4833 Fax: +82-53-426-7345E-mail: inkim@knu.ac.kr

Reference Figure

ET (+)ET (+) 6.0 5.5 5.0 4.5 4.0 6.0 5.5 5.0 4.5 4.0 (a)(b)***

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Reference Fig. 1**

2Reference Fig. 1. Effect of various antagonists on vascular relaxation induced by 17-estradiol (E2) or GPR30 agonist G1. E2 (a) or G1 (b) were added cumulatively to elicit relaxation when vascular contraction induced by U46619 (30 nmol/L) reached plateaus in endothelium-intact rat aortic rings pretreated with the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME, 100 mol/L), the ER/ER antagonist ICI 182,780 (10 mol/L), the ER-specific antagonist methyl-piperidino-pyrazole (MPP, 100 mol/L) or vehicle (0.1% DMSO) for 30 minutes. Relaxation is expressed as a percentage of the maximal contraction. Data are expressed as mean SEM. Data were analyzed by repeated measures ANOVA followed by Tukeys test (n=4 per group). One asterisk (*) P < 0.05, two asterisks (**) P < 0.01 vs. vehicle. 1.0 3.0 10 3010030 nmol/L U46619G1 (mol/L) KCl 020(mN)SNP (100 nmol/L)30 nmol/L U46619G1 (mol/L) KCl 020(mN) 1.0 3.0 1030100SNP (100 nmol/L)(a)(b)ET (+)ET (-)Reference Fig. 2Reference Fig. 2. Effect of sodium nitroprusside (SNP) on vascular relaxation induced by GPR30 agonist G1. Representative traces show relaxing responses to SNP. G1 was added cumulatively to elicit relaxation when vascular contraction induced by U46619 (30 nmol/L) reached plateaus in endothelium-intact (a) or denuded (b) rat aortic rings. The addition of G1 was followed by 100 nmol/L SNP.

ET (+) 6.0 5.5 5.0 4.5 4.0 ***Reference Fig. 3#**#6Reference Fig. 3. Effect of GPR30 antagonist G15 on vascular relaxation induced by GPR30 agonist G1. G1 was added cumulatively to elicit relaxation when vascular contraction induced by U46619 (30 nmol/L) reached plateaus in endothelium-intact rat aortic rings pretreated with the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME, 100 mol/L), L-NAME and G15 (100 mol/L), G15 alone or vehicle (0.1% DMSO) for 30 minutes. Relaxation is expressed as a percentage of the maximal contraction. Data are expressed as mean SEM. Data were analyzed by repeated measures ANOVA followed by Tukeys test (n=4 per group). One asterisk (*) P < 0.05, two asterisks (**) P < 0.01 vs. vehicle. One number sign (#) P < 0.05 vs. L-NAME alone.

ET (-)ET (-)

ET (+)

ET (+) 6.0 5.5 5.0 4.5 4.0 6.0 5.5 5.0 4.5 4.0 6.0 5.5 5.0 4.5 4.0 6.0 5.5 5.0 4.5 4.0 (a)(c)(b)(d)Reference Fig. 4**

*****8Reference Fig. 4. Effect of soluble guanylate cyclase blocker 1H-[1,2,4]-oxadizolo[4,3-a]quinoxalin-1-one (ODQ) on vascular relaxation induced by 17-estradiol (E2) or GPR30 agonist G1. E2 or G1 were added cumulatively to elicit relaxation when vascular contraction induced by U46619 (30 nmol/L) reached plateaus in endothelium-intact [ET (+), a and b] or -denuded [ET (-), c and d] rat aortic rings pretreated with ODQ (1.0, or 10 mol/L) or vehicle (0.1% DMSO) for 30 minutes. Relaxation is expressed as a percentage of the maximal contraction. Data are expressed as mean SEM. Data were analyzed by repeated measures ANOVA followed by Tukeys test (n=4). One asterisk (*) P < 0.05, two asterisks (**) P < 0.01 vs. vehicle.

Reference Fig. 517-Estradiol attenuates vascular contraction through inhibition of RhoA/Rho kinase pathway. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jul;380(1):35-44. *

Reference Fig. 6

(a)(b) 6.0 5.5 5.0 4.5 4.0 6.0 5.5 5.0 4.5 4.0 *

ET (+)ET (+)11Reference Fig. 6. Effect of various antagonists on vascular relaxation induced by 17-estradiol (E2). E2 was added cumulatively to elicit relaxation when vascular contraction induced by U46619 (30 nmol/L) reached plateaus in endothelium-intact rat aortic rings pretreated with the phosphatidylinositol 3-kinase inhibitor LY294002 (10 mol/L, a), the phosphatidylinositol 3-kinase inert LY analogue LY303511 (10 mol/L, a), the cAMP-dependent protein kinase inhibitor H89 (10 mol/L, b), or vehicle (0.1% DMSO) for 30 minutes. Relaxation is expressed as a percentage of the maximal contraction. Data are expressed as mean SEM. Data were analyzed by repeated measures ANOVA followed by Tukeys test (n=4 per group). One asterisk (*) P < 0.05 vs. vehicle. 020(mN) 020(mN) 020(mN)KClKClKCl30 nmol/L U46619Isoproterenol (mol/L)30 nmol/L U46619Isoproterenol (mol/L)30 nmol/L U46619Isoproterenol (mol/L)Vehicle (DMSO)1.0 mol/L H8910 mol/L H89 0.01 0.1 1.0 0.01 0.1 10 0.01 0.110 100 1.0100 1.0 10 100 (a)Reference Fig. 7ET (+)30 nmol/L U46619Isoproterenol (mol/L)Vehicle (DMSO) 0.01 0.1 1.0 10 100 KCl 020(mN)1.0 mol/L H8930 nmol/L U46619Isoproterenol (mol/L) 0.01 0.1 1.0 10 100 KCl 020(mN)10 mol/L H8930 nmol/L U46619Isoproterenol (mol/L) 0.01 0.1 1.0 10 100 KCl 020(mN)(b)Reference Fig. 7ET (-)Reference Fig. 7. Effect of cAMP-dependent protein kinase inhibitor H89 on vascular relaxation induced by cAMP-dependent agent isoproterenol. Representative traces show relaxing responses. Isoproterenol was added cumulatively to elicit relaxation when vascular contraction induced by U46619 (30 nmol/L) reached plateaus in endothelium-intact (a) or -denuded (b) rat aortic rings pretreated with H89 (1.0 or 10 mol/L) or vehicle (0.1% DMSO) for 30 minutes.

Protein kinase A-dependent and -independent effects of isoproterenol in rat isolated mesenteric artery: interactions with levcromakalim.J Pharmacol Exp Ther. 2001 Sep;298(3):917-24.Reference Fig. 8

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