OBJECTIVES: This study investigated the signalling mechanism of the relaxant responses to the estrogen receptor (ERalpha) agonist PPT (propyl pyrazole triol) in endothelium-denuded rat aortic rings. METHODS: Several compounds, including protein kinase G (PKG) inhibitors and potassium channel inhibitors, were tested against PPT-dependent rat aortic relaxation. Cyclic GMP and cytosolic calcium responses to PPT in isolated aortic smooth muscle were investigated in parallel. KEY FINDINGS: PPT vasorelaxation was largely reduced by the selective ERalpha antagonist methyl-piperidinopyrazole (MPP; -91.6+/-2.5%), by the selective PKG inhibitor Rp-8-Br-cGMP (-78.6+/-4.9%), by the specific soluble guanylyl cyclase inhibitor ODQ (1H-(1,2,4)-oxadiazolo[4,3-a]quinoxalin-1-one; -85.3+/-5.2%) and to a lesser extent by the selective BKCa (large-conductance calcium- and voltage-activated potassium channel) inhibitor iberiotoxin (-59.3%), the selective IKCa (intermediate-conductance calcium-activated potassium channel) inhibitor TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole; -50.7%) and the voltage-gated potassium channel inhibitor 4-aminopyridine (-40.8%). In isolated aortic smooth muscle, PPT strongly enhanced the cyclic GMP content (+144%) and Rp-8-Br-cGMP largely reduced the PPT-dependent calcium signal (-80.8%). CONCLUSIONS: ERalpha receptor stimulation in rat aortic smooth muscle evokes a PKG-signalling pathway, likely triggering relaxation by BKCa and IKCa channel opening.
OBJECTIVES: This study investigated the signalling mechanism of the relaxant responses to the estrogen receptor (ERalpha) agonist PPT (propyl pyrazole triol) in endothelium-denuded rat aortic rings. METHODS: Several compounds, including protein kinase G (PKG) inhibitors and potassium channel inhibitors, were tested against PPT-dependent rat aortic relaxation. Cyclic GMP and cytosolic calcium responses to PPT in isolated aortic smooth muscle were investigated in parallel. KEY FINDINGS:PPT vasorelaxation was largely reduced by the selective ERalpha antagonist methyl-piperidinopyrazole (MPP; -91.6+/-2.5%), by the selective PKG inhibitor Rp-8-Br-cGMP (-78.6+/-4.9%), by the specific soluble guanylyl cyclase inhibitor ODQ (1H-(1,2,4)-oxadiazolo[4,3-a]quinoxalin-1-one; -85.3+/-5.2%) and to a lesser extent by the selective BKCa (large-conductance calcium- and voltage-activated potassium channel) inhibitor iberiotoxin (-59.3%), the selective IKCa (intermediate-conductance calcium-activated potassium channel) inhibitor TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole; -50.7%) and the voltage-gated potassium channel inhibitor 4-aminopyridine (-40.8%). In isolated aortic smooth muscle, PPT strongly enhanced the cyclic GMP content (+144%) and Rp-8-Br-cGMP largely reduced the PPT-dependent calcium signal (-80.8%). CONCLUSIONS:ERalpha receptor stimulation in rat aortic smooth muscle evokes a PKG-signalling pathway, likely triggering relaxation by BKCa and IKCa channel opening.
Authors: Fernando P Filgueira; Núbia S Lobato; Denise L Nascimento; Graziela S Ceravolo; Fernanda R C Giachini; Victor V Lima; Ana Paula Dantas; Zuleica B Fortes; R Clinton Webb; Rita C Tostes; Maria Helena C Carvalho Journal: Steroids Date: 2018-11-17 Impact factor: 2.668
Authors: Karina M Mata; Wei Li; Ossama M Reslan; Waleed T Siddiqui; Lauren A Opsasnick; Raouf A Khalil Journal: Am J Physiol Heart Circ Physiol Date: 2015-09-25 Impact factor: 4.733
Authors: Aida Oliván-Viguera; Marta Sofía Valero; Estéfano Pinilla; Sara Amor; Ángel Luis García-Villalón; Nichole Coleman; Celia Laría; Víctor Calvín-Tienza; Ángel-Luis García-Otín; José M Fernández-Fernández; M Divina Murillo; José A Gálvez; María D Díaz-de-Villegas; Ramón Badorrey; Ulf Simonsen; Luis Rivera; Heike Wulff; Ralf Köhler Journal: Basic Clin Pharmacol Toxicol Date: 2016-02-29 Impact factor: 4.080
Authors: Debrabata Chanda; Jesus Prieto-Lloret; Arjun Singh; Hina Iqbal; Pankaj Yadav; Vladimir Snetkov; Philip I Aaronson Journal: Life Sci Date: 2016-09-26 Impact factor: 5.037