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Arch Biochem Biophys ; 478(2): 136-42, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18708025

RESUMO

Increasing evidence from both clinical and experimental studies indicates that the insulin-releasing hormone, glucagon-like peptide-1 (GLP-1) may exert additional protective/reparative effects on the cardiovascular system. The aim of this study was to examine vasorelaxant effects of GLP-1(7-36)amide, three structurally-related peptides and a non-peptide GLP-1 agonist in rat aorta. Interestingly, all GLP-1 compounds, including the established GLP-1 receptor antagonist, exendin (9-39) caused concentration-dependent relaxation. Mechanistic studies employing hyperpolarising concentrations of potassium or glybenclamide revealed that these relaxant effects are mediated via specific activation of ATP-sensitive potassium channels. Further experiments using a specific membrane-permeable cyclic AMP (cAMP) antagonist, and demonstration of increased cAMP production in response to GLP-1 illustrated the critical importance of this pathway. These data significantly extend previous observations suggesting that GLP-1 may modulate vascular function, and indicate that this effect may be mediated by the GLP-1 receptor. However, further studies are required in order to establish whether GLP-1 related agents may confer additional cardiovascular benefits to diabetic patients.


Assuntos
Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , AMP Cíclico/fisiologia , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Canais KATP/fisiologia , Animais , Primers do DNA/genética , Expressão Gênica , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Receptor do Peptídeo Semelhante ao Glucagon 1 , Técnicas In Vitro , Masculino , Fragmentos de Peptídeos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Glucagon/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
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