nÃo hà / A Alpinia zerumbet à uma planta comumente encontrada na regiÃo do nordeste do Brasil. Essa planta à conhecida popularmente por colÃnia e à muito utilizada na medicina popular por suas propriedades diurÃticas e anti-hipertensivas. O objetivo do presente estudo foi investigar se o extrato aquoso das folhas de A. zerumbet (EAAz) apresentava atividade vasodilatadora em aorta de rato prÃ-contraÃda com fenilefrina e, elucidar o seu mecanismo de aÃÃo. Ratos machos Wistar (250 a 300 g), provenientes do biotÃrio da UFC, foram sacrificados por deslocamento cervical e a aorta torÃcica removida e dissecada. Os anÃis da aorta (4 a 5 mm) foram montados em cÃmeras orgÃnicas, contendo soluÃÃo de Krebs e aerados com carbogÃnio a 37ÂC, para as medidas de variaÃÃes na tensÃo isomÃtrica. O endotÃlio dos anÃis da aorta foi removido mecanicamente para estudar o seu envolvimento no efeito vasodilatador do EAAz. Para estudar o envolvimento do Ãxido nÃtrico (NO), GMPc, prostanÃides, canais de potÃssio ativados por Ca2+, espÃcies reativas do oxigÃnio e a ativaÃÃo das enzimas quinases Src e PI3 quinase, as preparaÃÃes foram tratadas, respectivamente, com L-NAME (100 ÂM), ODQ (10 ÂM), indometacina (10 ÂM), caribdotoxina (100 nM) mais apamina (100 nM), MnTMPyP (100 ÂM), catalase (500 U/ml), PEG-catalase (500 U/ml), SOD (500 U/ml) e PP2 (20 ÂM), Wortmannin (300 nM). O efeito vasodilatador do EAAz (0,05; 0,15; 0,5; 1,5; 15 e 50 Âg/mL), acetilcolina (10-8 - 10-5 M) e nitroprussiato de sÃdio (10-8 M) foram avaliados em aorta de ratos prÃ-contraÃda com fenilefrina (10-8 - 3x10-8 M), antes e apÃs tratamento com os inibidores especÃficos. A vasodilataÃÃo induzida pelo EAAz mostrou-se dependente do endotÃlio e mediada pelo NO via GMPc jà que o relaxamento vascular foi abolido na presenÃa do Ãster metÃlico de NG-nitro-l-arginina e do ODQ. A vasodilataÃÃo tambÃm foi reduzida pelo MnTMPyP (permeante celular mimÃtico da SOD), polietilenoglicol catalase, PP2 (inibidor da quinase Src) e Wortmannin (inibidor da fosfoinositideo 3-quinases). A via de produÃÃo de EROs induzida pelo EAAz foi inibida significativamente pela aÃÃo do MnTMPyP e PEG-catalase. Ocorreu tambÃm a inibiÃÃo da via EROs/PI3 quinase/Src quinase que estÃo envolvidas na ativaÃÃo da eNOS. O EAAz causou um relaxamento dependente do endotÃlio via NO/GMPc com o possÃvel envolvimento de EROs e das Src quinase e fosfoinositideo 3-quinase dependente de Akt. Dessa forma, pode-se concluir que o relaxamento vascular induzido pelo EAAz poderia explicar o tradicional uso do chà das folhas de A. zerumbet para o tratamento da hipertensÃo arterial. / The Alpinia zerumbet is a plant commonly found in the northeastern region of Brazil. This plant is popularly known as colony and is widely used in folk medicine for its diuretic and antihypertensive properties. The aim of this study was to investigate whether the aqueous extract of leaves of A. zerumbet (EAAz) had vasodilator activity in rat aorta pre-contracted with phenylephrine and to elucidate its mechanism of action. Male Wistar rats (250-300 g) from the vivarium of UFC, were killed by cervical dislocation and the thoracic aorta removed and dissected. The aortic rings (4-5 mm) were mounted in organ cameras, and containing Krebs solution aerated with carbogen at 37  C to measure changes in isometric tension. The endothelium of the aortic rings was removed mechanically to study their involvement in the vasodilator effect of EAAz. To study the involvement of nitric oxide (NO), cGMP, prostanoid, potassium channels activated by Ca2+, reactive oxygen species and activation of enzymes kinases Src and PI3 kinase, the preparations were treated respectively with L-NAME (100 ÂM ), ODQ (10 ÂM), indomethacin (10 ÂM), carybdotoxin (100 nM) plus apamin (100 nM), MnTMPyP (100 ÂM), catalase (500 U / ml), PEG-catalase (500 U/ ml), SOD (500 U / ml) and PP2 (20 ÂM), wortmannin (300 nM). The vasodilatory effect of EAAz (0.05, 0.15, 0.5, 1.5, 15 and 50 Âg / mL), acetylcholine (10-8 - 10-5 M) and sodium nitroprusside (10-8 M ) were evaluated in the aorta of rats pre-contracted with phenylephrine (10-8 - 3x10-8 M) before and after treatment with the specific inhibitors. EAAz induced vasodilation was dependent and endothelium mediated by NO via cGMP as the vascular relaxation was abolished in the presence of the methyl ester of NG-nitro-L-arginine and ODQ. Vasodilation was also reduced by MnTMPyP (mimetic cellular permeant SOD), catalase polyethylene glycol, PP2 (Src kinase inhibitor) and wortmannin (inhibitor of phosphoinositide 3-kinase). The route of production of ROS induced EAAz was significantly prevented by the action of MnTMPyP and PEG-catalase. There was also the inhibition of the kinase ROS/PI3 / Src kinase that are involved in the activation of the eNOS. The EAAz caused an endothelium-dependent relaxation via NO / cGMP with the possible involvement of ROS and Src kinase and phosphoinositide 3-kinase-dependent Akt. Taking us to the conclusion that the vascular relaxation induced by EAAz could explain the traditional use of the tea leaves of A. zerumbet for the treatment of hypertension.
Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:9842 |
Date | 14 April 2012 |
Creators | Hidemburgo Goncalves Rocha |
Contributors | Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, Danielle MacÃdo Gaspar, FlÃvia Almeida Santos, Hemerson Iury Ferreira MagalhÃes |
Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em Farmacologia, UFC, BR |
Source Sets | IBICT Brazilian ETDs |
Language | Portuguese |
Detected Language | English |
Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
Format | application/pdf |
Source | reponame:Biblioteca Digital de Teses e Dissertações da UFC, instname:Universidade Federal do Ceará, instacron:UFC |
Rights | info:eu-repo/semantics/openAccess |
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