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Abstract(s)
Globalmente, as doenças cardiovasculares são consideradas umas das principais causas de morbilidade e mortalidade. O papel dos androgénios no envolvimento destas doenças tem vindo a ser estudado e evidenciam um efeito protetor sobre o sistema cardiovascular. Diversos estudos indicam que a testosterona possui um efeito vasodilatador sobre diversos vasos sanguíneos, incluindo a artéria umbilical humana. Este efeito é mediado pela ativação da PKG que posteriormente ativa os canais BKCa e KV. Estudos recentes demonstram que os efeitos genómicos dos androgénios promovem alterações nas subunidades dos canais iónicos, nomeadamente na subunidade ß1 dos canais BKCa e na subunidade a1c dos canais de Ca2+ tipo L. Estas modificações parecem influenciar a funcionalidade destes canais. O principal objetivo deste trabalho foi analisar os efeitos genómicos dos androgénios nas células musculares lisas de artérias umbilicais humanas a nível da atividade dos canais de potássio.
Utilizou-se técnica de Patch-clamp para analisar a corrente de potássio nas células musculares lisas da artéria umbilical. Foi estudado o efeito de diferentes inibidores de canais de potássio em células incubadas e não incubadas com DHT (10nM) para posterior comparação. Estudou-se também o efeito dos androgénios nestas células a nível da contratilidade através da técnica de PCSA. Foram utilizadas células não incubadas e incubadas com DHT (10nM) e adicionados inibidores de proteínas cinases (KTa e KTg) de modo a averiguar se o efeito sobre a PKA e PKG seria igual em efeitos genómicos.
Os resultados demonstram que a corrente de K+ observada em HUASMC é devida aos canais BKCa e KV e que os efeitos genómicos dos androgénios envolvem a ativação de canais KV. Também se verificou que a adição da KTg promove uma diminuição no relaxamento induzido pelo ANP e SNP, por conseguinte o efeito vasodilatador do SNP e ANP envolve a ativação da PKG. Finalmente demonstrou-se que os efeitos genómicos e não genómicos dos androgénios contribuem para o mesmo efeito.
Assim, os efeitos genómicos dos androgénios na atividade dos canais de potássio mostraram ser dependentes dos canais KV e similares aos efeitos não genómicos.
Globally cardiovascular diseases are considered a major cause of morbidity and mortality. The role played by androgens in these diseases has been studied and evidences a protective effect on the cardiovascular system. Several studies indicate that testosterone has a vasodilatory effect on various blood vessels, including the human umbilical artery. This effect is mediated by activation of PKG which subsequently activates BKCa and KV channels. Recent studies show that the genomic effects of androgens promote changes in ion channel subunits, including ß1 subunit of the BKCa channels and a1c subunit of the L-type Ca2+ channels. These changes appear to influence the functioning of these channels. The main objective of this work was to analyze the genomic effects of androgens on smooth muscle cells of the human umbilical arteries at the level of activity of potassium channels. Patch-clamp technique was used to analyze the potassium current in smooth muscle cells from the umbilical artery. The effect of different potassium channels inhibitors was studied in cells incubated and not incubated with DHT (10 nM) for comparison. Also studied was the effect of androgens in these cells at the level of contractility throught the PCSA technique. Cells which were incubated with DHT (10 nM) and cells which were not incubated were used and added protein kinase inhibitors (KTa and KTg) in order to determine that the effect on PKA and PKG is equal in genomic effects. The results demonstrate that the K+ current in HUASMC is due to the BKCa and KV channels and genomic effects of androgens involving activation of KV channels. Another conclusion was that the addition of KTg promotes a decrease in the relaxation induced by SNP and ANP, so the vasodilator effect of SNP and ANP involve the activation of PKG. Finally it was proved that genomic and non-genomic effects of androgen contribute to the same effect. Thus, the genomic effects of androgens on the activity of potassium channels are dependent on KV channels and similars to the non-genomic effects.
Globally cardiovascular diseases are considered a major cause of morbidity and mortality. The role played by androgens in these diseases has been studied and evidences a protective effect on the cardiovascular system. Several studies indicate that testosterone has a vasodilatory effect on various blood vessels, including the human umbilical artery. This effect is mediated by activation of PKG which subsequently activates BKCa and KV channels. Recent studies show that the genomic effects of androgens promote changes in ion channel subunits, including ß1 subunit of the BKCa channels and a1c subunit of the L-type Ca2+ channels. These changes appear to influence the functioning of these channels. The main objective of this work was to analyze the genomic effects of androgens on smooth muscle cells of the human umbilical arteries at the level of activity of potassium channels. Patch-clamp technique was used to analyze the potassium current in smooth muscle cells from the umbilical artery. The effect of different potassium channels inhibitors was studied in cells incubated and not incubated with DHT (10 nM) for comparison. Also studied was the effect of androgens in these cells at the level of contractility throught the PCSA technique. Cells which were incubated with DHT (10 nM) and cells which were not incubated were used and added protein kinase inhibitors (KTa and KTg) in order to determine that the effect on PKA and PKG is equal in genomic effects. The results demonstrate that the K+ current in HUASMC is due to the BKCa and KV channels and genomic effects of androgens involving activation of KV channels. Another conclusion was that the addition of KTg promotes a decrease in the relaxation induced by SNP and ANP, so the vasodilator effect of SNP and ANP involve the activation of PKG. Finally it was proved that genomic and non-genomic effects of androgen contribute to the same effect. Thus, the genomic effects of androgens on the activity of potassium channels are dependent on KV channels and similars to the non-genomic effects.
Description
Keywords
Androgénios Artéria Umbilical Humana Canais de Potássio Células Musculares Lisas Efeitos Genómicos Guanilato Ciclase Membranar. Proteína Cinase G