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| Curriculum Vitae | 17.52 MB | Adobe PDF | ||
| Tese | 2.32 MB | Adobe PDF |
Advisor(s)
Abstract(s)
Diversos estudos indicam que o risco de desenvolvimento de Doença Arterial Coronária
e Hipertensão é superior nos homens do que em mulheres pré-menopausa. Postula-se
que seja resultado de efeitos desfavoráveis da hormona testosterona. No entanto esta
mostrou ter efeitos não genómicos vasodilatadores, que podem estar envolvidos num
efeito protectivo, mas este assunto ainda não está clarificada.
Foi estudado a acção da testosterona e do colesterol nos canais de cálcio tipo L e nos
canais de potássio nas células A7r5. O efeito da testosterona nos canais activados por
nucleótidos cíclicos foi também estudado nas células musculares lisas da artéria
umbilical humana. Para tal foi utilizado um sistema de patch clamp. A testosterona e o
colesterol inibiram as correntes de cálcio tipo L, tanto basais como estimuladas por Bay
K8644, de forma concentração-dependente. As correntes de potássio não sofreram
alterações significativas. A testosterona foi também capaz de activar as correntes de
canais de CNG.
Tendo em conta os resultados obtidos, podemos afirmar que a testosterona e colesterol
induzem relaxação nas células de músculo liso de aorta de rato. Estes dados sugerem
que estes esteróides partilham um mecanismo de acção comum nestas células, estando
nele envolvido a inactivação dos canais de cálcio, LTCCs.
Nas células do músculo liso vascular da artéria umbilical humana verificou-se um
aumento do cGMP, indicando que o mecanismo envolvido na relaxação pela
testosterona envolve a via do cGMP.
Several studies point out the increased risk in men versus pre-menopause women on developing coronary artery disease and hypertension. This is, nowadays, seen as a result of unfavourable efects of testosterone. However, this hormone showed non-genomic vasodilator effects which may be involved in some kind of protection, yet this matter isn't clarified. We studied the action of testosterone and cholesterol on A7r5 cells L-type calcium channels and potassium channels. The effect of testosterone on cyclic nucleotide activated channels has been also studied, using smooth muscle cells from human umbilical artery. To do this, we used a patch clamp system. Testosterone and cholesterol inhibited L-type calcium channels, basal as well when stimulated with Bay K8644, in a concentration-dependent way. Potassium currents haven't suffered significative changes. Testosterone was also able to activate CNG channels currents. According to these results, we can say that testosterone and cholesterol induce relaxation in rat aorta (muscle?) cells. These data suggest that these steroids share a common mechanism of action on rat aorta, being involved the inactivation of calcium channels, the LTCC's. On vascular smooth muscle cells from human umbilical artery was identified an increase of cGMP, showing that the mechanism involved in testosterone induced relaxation uses cGMP pathway.
Several studies point out the increased risk in men versus pre-menopause women on developing coronary artery disease and hypertension. This is, nowadays, seen as a result of unfavourable efects of testosterone. However, this hormone showed non-genomic vasodilator effects which may be involved in some kind of protection, yet this matter isn't clarified. We studied the action of testosterone and cholesterol on A7r5 cells L-type calcium channels and potassium channels. The effect of testosterone on cyclic nucleotide activated channels has been also studied, using smooth muscle cells from human umbilical artery. To do this, we used a patch clamp system. Testosterone and cholesterol inhibited L-type calcium channels, basal as well when stimulated with Bay K8644, in a concentration-dependent way. Potassium currents haven't suffered significative changes. Testosterone was also able to activate CNG channels currents. According to these results, we can say that testosterone and cholesterol induce relaxation in rat aorta (muscle?) cells. These data suggest that these steroids share a common mechanism of action on rat aorta, being involved the inactivation of calcium channels, the LTCC's. On vascular smooth muscle cells from human umbilical artery was identified an increase of cGMP, showing that the mechanism involved in testosterone induced relaxation uses cGMP pathway.
Description
Keywords
Testosterona Testosterona - Canais iónicos Colesterol - Canais iónicos Artéria umbilical humana
Citation
Publisher
Universidade da Beira Interior