Mechanisms involved in the vasodilator effect induced by diosgenin in rat superior mesenteric artery

The aim of this study was to investigate the vasorelaxant effect induced by diosgenin in superior mesenteric rings. In rings pre-contracted with phenylephrine (10μM), diosgenin caused concentration-dependent relaxations [EC 50 = (3.3 ± 1.2) × 10 − 4M, E max = 94.2 ± 2.6 %]. Vascular relaxation induc...

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Veröffentlicht in:European journal of pharmacology 2007-11, Vol.574 (2), p.172-178
Hauptverfasser: Dias, Katy Lísias Gondim, Correia, Nadja de Azevedo, Pereira, Krísthea Karyne Gonçalves, Barbosa-Filho, José Maria, Cavalcante, Karla Veruska Marques, Araújo, Islania Giselia Albuquerque, Silva, Darizy Flávia, Guedes, Diego Nunes, Neto, Mario dos Anjos, Bendhack, Lusiane Maria, Medeiros, Isac Almeida
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container_issue 2
container_start_page 172
container_title European journal of pharmacology
container_volume 574
creator Dias, Katy Lísias Gondim
Correia, Nadja de Azevedo
Pereira, Krísthea Karyne Gonçalves
Barbosa-Filho, José Maria
Cavalcante, Karla Veruska Marques
Araújo, Islania Giselia Albuquerque
Silva, Darizy Flávia
Guedes, Diego Nunes
Neto, Mario dos Anjos
Bendhack, Lusiane Maria
Medeiros, Isac Almeida
description The aim of this study was to investigate the vasorelaxant effect induced by diosgenin in superior mesenteric rings. In rings pre-contracted with phenylephrine (10μM), diosgenin caused concentration-dependent relaxations [EC 50 = (3.3 ± 1.2) × 10 − 4M, E max = 94.2 ± 2.6 %]. Vascular relaxation induced by diosgenin was significantly inhibited after removal of the endothelium ( E max = 46 ± 8.8%, p < 0.001) or after pre-treatment of the rings with N-nitro- l-arginine methyl esther ( l-NAME) 100 or 300μM ( E max = 35.3 ± 4%; 28.1 ± 3.3%, respectively, p < 0.001), atropine 1μM ( E max = 24.6 ± 3.4%, p < 0.001), hydroxocobalamin 30μM ( E max = 54.0 ± 9.6%, p < 0.001), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) 10μM ( E max = 46.0 ± 8.0%, p < 0.001) or indomethacin 1μM ( E max = 22.6 ± 11.8%, p < 0.001). Vasorelaxation evoked by diosgenin was significantly inhibited after pre-treatment of preparations with both selective and non-selective inhibitors of large conductance Ca 2+-activated K + (BK Ca) channels, iberiotoxin 100nM or tetraethylammonium (TEA) 1mM, respectively ( E max = 62.5 ± 9.1%; 65.7 ± 1.1%, p < 0.001). Conversely, in endothelium-denuded vessels, none of BK Ca channel blockers modified the relaxant effect induced by diosgenin. In mesenteric endothelial cells loaded with FURA-2 diosgenin was able to increase intracellular calcium concentrations, which were significantly decreased by atropine 1μM. In addition, in isolated mesenteric rings, diosgenin induced marked increase in nitric oxide (NO) levels, which was completely abolished after functional endothelium removal. The results obtained here demonstrated that diosgenin-induced relaxation appears to involve endothelial muscarinic receptor activation with increase in intracellular calcium concentrations and consequent release of endothelium-derived relaxing factors (EDRFs), mainly NO and cyclooxygenase derivatives, which activate BK Ca channels. Nevertheless, further studies are necessary to clearly elucidate residual endothelium-independent relaxation induced by diosgenin.
doi_str_mv 10.1016/j.ejphar.2007.07.017
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In rings pre-contracted with phenylephrine (10μM), diosgenin caused concentration-dependent relaxations [EC 50 = (3.3 ± 1.2) × 10 − 4M, E max = 94.2 ± 2.6 %]. Vascular relaxation induced by diosgenin was significantly inhibited after removal of the endothelium ( E max = 46 ± 8.8%, p < 0.001) or after pre-treatment of the rings with N-nitro- l-arginine methyl esther ( l-NAME) 100 or 300μM ( E max = 35.3 ± 4%; 28.1 ± 3.3%, respectively, p < 0.001), atropine 1μM ( E max = 24.6 ± 3.4%, p < 0.001), hydroxocobalamin 30μM ( E max = 54.0 ± 9.6%, p < 0.001), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) 10μM ( E max = 46.0 ± 8.0%, p < 0.001) or indomethacin 1μM ( E max = 22.6 ± 11.8%, p < 0.001). Vasorelaxation evoked by diosgenin was significantly inhibited after pre-treatment of preparations with both selective and non-selective inhibitors of large conductance Ca 2+-activated K + (BK Ca) channels, iberiotoxin 100nM or tetraethylammonium (TEA) 1mM, respectively ( E max = 62.5 ± 9.1%; 65.7 ± 1.1%, p < 0.001). Conversely, in endothelium-denuded vessels, none of BK Ca channel blockers modified the relaxant effect induced by diosgenin. In mesenteric endothelial cells loaded with FURA-2 diosgenin was able to increase intracellular calcium concentrations, which were significantly decreased by atropine 1μM. In addition, in isolated mesenteric rings, diosgenin induced marked increase in nitric oxide (NO) levels, which was completely abolished after functional endothelium removal. The results obtained here demonstrated that diosgenin-induced relaxation appears to involve endothelial muscarinic receptor activation with increase in intracellular calcium concentrations and consequent release of endothelium-derived relaxing factors (EDRFs), mainly NO and cyclooxygenase derivatives, which activate BK Ca channels. 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In rings pre-contracted with phenylephrine (10μM), diosgenin caused concentration-dependent relaxations [EC 50 = (3.3 ± 1.2) × 10 − 4M, E max = 94.2 ± 2.6 %]. Vascular relaxation induced by diosgenin was significantly inhibited after removal of the endothelium ( E max = 46 ± 8.8%, p < 0.001) or after pre-treatment of the rings with N-nitro- l-arginine methyl esther ( l-NAME) 100 or 300μM ( E max = 35.3 ± 4%; 28.1 ± 3.3%, respectively, p < 0.001), atropine 1μM ( E max = 24.6 ± 3.4%, p < 0.001), hydroxocobalamin 30μM ( E max = 54.0 ± 9.6%, p < 0.001), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) 10μM ( E max = 46.0 ± 8.0%, p < 0.001) or indomethacin 1μM ( E max = 22.6 ± 11.8%, p < 0.001). Vasorelaxation evoked by diosgenin was significantly inhibited after pre-treatment of preparations with both selective and non-selective inhibitors of large conductance Ca 2+-activated K + (BK Ca) channels, iberiotoxin 100nM or tetraethylammonium (TEA) 1mM, respectively ( E max = 62.5 ± 9.1%; 65.7 ± 1.1%, p < 0.001). Conversely, in endothelium-denuded vessels, none of BK Ca channel blockers modified the relaxant effect induced by diosgenin. In mesenteric endothelial cells loaded with FURA-2 diosgenin was able to increase intracellular calcium concentrations, which were significantly decreased by atropine 1μM. In addition, in isolated mesenteric rings, diosgenin induced marked increase in nitric oxide (NO) levels, which was completely abolished after functional endothelium removal. The results obtained here demonstrated that diosgenin-induced relaxation appears to involve endothelial muscarinic receptor activation with increase in intracellular calcium concentrations and consequent release of endothelium-derived relaxing factors (EDRFs), mainly NO and cyclooxygenase derivatives, which activate BK Ca channels. Nevertheless, further studies are necessary to clearly elucidate residual endothelium-independent relaxation induced by diosgenin.]]></description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Diosgenin</subject><subject>Diosgenin - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endothelium-Dependent Relaxing Factors - physiology</subject><subject>Intracellular Ca 2</subject><subject>Large-Conductance Calcium-Activated Potassium Channels - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mesenteric artery</subject><subject>Mesenteric Artery, Superior - drug effects</subject><subject>Mesenteric Artery, Superior - physiology</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - physiology</subject><subject>Pharmacology. 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Drug treatments</topic><topic>Phenylephrine - pharmacology</topic><topic>Potassium Channel Blockers - pharmacology</topic><topic>Prostaglandin-Endoperoxide Synthases - physiology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Vasodilation</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dias, Katy Lísias Gondim</creatorcontrib><creatorcontrib>Correia, Nadja de Azevedo</creatorcontrib><creatorcontrib>Pereira, Krísthea Karyne Gonçalves</creatorcontrib><creatorcontrib>Barbosa-Filho, José Maria</creatorcontrib><creatorcontrib>Cavalcante, Karla Veruska Marques</creatorcontrib><creatorcontrib>Araújo, Islania Giselia Albuquerque</creatorcontrib><creatorcontrib>Silva, Darizy Flávia</creatorcontrib><creatorcontrib>Guedes, Diego Nunes</creatorcontrib><creatorcontrib>Neto, Mario dos Anjos</creatorcontrib><creatorcontrib>Bendhack, Lusiane Maria</creatorcontrib><creatorcontrib>Medeiros, Isac Almeida</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dias, Katy Lísias Gondim</au><au>Correia, Nadja de Azevedo</au><au>Pereira, Krísthea Karyne Gonçalves</au><au>Barbosa-Filho, José Maria</au><au>Cavalcante, Karla Veruska Marques</au><au>Araújo, Islania Giselia Albuquerque</au><au>Silva, Darizy Flávia</au><au>Guedes, Diego Nunes</au><au>Neto, Mario dos Anjos</au><au>Bendhack, Lusiane Maria</au><au>Medeiros, Isac Almeida</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms involved in the vasodilator effect induced by diosgenin in rat superior mesenteric artery</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2007-11-28</date><risdate>2007</risdate><volume>574</volume><issue>2</issue><spage>172</spage><epage>178</epage><pages>172-178</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract><![CDATA[The aim of this study was to investigate the vasorelaxant effect induced by diosgenin in superior mesenteric rings. In rings pre-contracted with phenylephrine (10μM), diosgenin caused concentration-dependent relaxations [EC 50 = (3.3 ± 1.2) × 10 − 4M, E max = 94.2 ± 2.6 %]. Vascular relaxation induced by diosgenin was significantly inhibited after removal of the endothelium ( E max = 46 ± 8.8%, p < 0.001) or after pre-treatment of the rings with N-nitro- l-arginine methyl esther ( l-NAME) 100 or 300μM ( E max = 35.3 ± 4%; 28.1 ± 3.3%, respectively, p < 0.001), atropine 1μM ( E max = 24.6 ± 3.4%, p < 0.001), hydroxocobalamin 30μM ( E max = 54.0 ± 9.6%, p < 0.001), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) 10μM ( E max = 46.0 ± 8.0%, p < 0.001) or indomethacin 1μM ( E max = 22.6 ± 11.8%, p < 0.001). Vasorelaxation evoked by diosgenin was significantly inhibited after pre-treatment of preparations with both selective and non-selective inhibitors of large conductance Ca 2+-activated K + (BK Ca) channels, iberiotoxin 100nM or tetraethylammonium (TEA) 1mM, respectively ( E max = 62.5 ± 9.1%; 65.7 ± 1.1%, p < 0.001). Conversely, in endothelium-denuded vessels, none of BK Ca channel blockers modified the relaxant effect induced by diosgenin. In mesenteric endothelial cells loaded with FURA-2 diosgenin was able to increase intracellular calcium concentrations, which were significantly decreased by atropine 1μM. In addition, in isolated mesenteric rings, diosgenin induced marked increase in nitric oxide (NO) levels, which was completely abolished after functional endothelium removal. The results obtained here demonstrated that diosgenin-induced relaxation appears to involve endothelial muscarinic receptor activation with increase in intracellular calcium concentrations and consequent release of endothelium-derived relaxing factors (EDRFs), mainly NO and cyclooxygenase derivatives, which activate BK Ca channels. Nevertheless, further studies are necessary to clearly elucidate residual endothelium-independent relaxation induced by diosgenin.]]></abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>17689524</pmid><doi>10.1016/j.ejphar.2007.07.017</doi><tpages>7</tpages></addata></record>
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subjects Animals
Biological and medical sciences
Calcium - metabolism
Diosgenin
Diosgenin - pharmacology
Dose-Response Relationship, Drug
Endothelium-Dependent Relaxing Factors - physiology
Intracellular Ca 2
Large-Conductance Calcium-Activated Potassium Channels - physiology
Male
Medical sciences
Mesenteric artery
Mesenteric Artery, Superior - drug effects
Mesenteric Artery, Superior - physiology
Nitric oxide
Nitric Oxide - physiology
Pharmacology. Drug treatments
Phenylephrine - pharmacology
Potassium Channel Blockers - pharmacology
Prostaglandin-Endoperoxide Synthases - physiology
Rats
Rats, Wistar
Vasodilation
Vasodilation - drug effects
Vasodilator Agents - pharmacology
title Mechanisms involved in the vasodilator effect induced by diosgenin in rat superior mesenteric artery
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