RESUMO
In the normal human adrenal gland, serotonin (5-HT) stimulates aldosterone secretion through the 5-HT4 receptor (5-HT4R). However, the physiological role of the serotonergic control of adrenocortical function is not known. In the present study, we have investigated the ability of l-Lysine, which has been shown to act as a 5-HT4 receptor antagonist, to counteract in vitro and in vivo the stimulatory effect of 5-HT4R agonists on aldosterone production. l-Lysine was found to inhibit aldosterone production induced by 5-HT and the 5-HT4R agonists BIMU8 from cultured human adrenocortical cells. The action of l-Lysine (4.95 g/day orally) on the adrenal cortex was also evaluated in 20 healthy volunteers in a double blind, cross-over, placebo controlled study. l-Lysine had no significant influence on basal plasma aldosterone levels and the aldosterone responses to upright posture, tetracosactide, and low sodium diet (10 mmol/day for 3 days). Conversely, l-Lysine significantly reduced the surge of plasma aldosterone induced by metoclopramide indicating that l-Lysine is able to efficiently antagonize the adrenal 5-HT4 receptors in vivo. These results suggest that l-Lysine supplementation may represent a new treatment of primary adrenal diseases in which corticosteroid hypersecretion is driven by overexpressed 5-HT4 receptors.
Assuntos
Doenças das Glândulas Suprarrenais/tratamento farmacológico , Glândulas Suprarrenais/metabolismo , Aldosterona/metabolismo , Lisina/administração & dosagem , Receptores 5-HT4 de Serotonina/metabolismo , Antagonistas do Receptor 5-HT4 de Serotonina/administração & dosagem , Serotoninérgicos/administração & dosagem , Doenças das Glândulas Suprarrenais/metabolismo , Doenças das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/patologia , Células Cultivadas , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Serotonina/metabolismoRESUMO
Daily urinary collection and assessment of glomerular filtration rate (GFR) and effective renal plasma flow were performed in ten 2-month-old Beagle puppies and ten 6-9 year-old Beagle dogs to identify age-associated differences in renal function. The most striking differences in puppies compared to mature dogs were a higher daily urinary volume (+65%), GFR (+87%), free water reabsorption (+159%), a lower daily protein excretion (-88%), and fractional excretion of phosphorus (-35%). Renal function in Beagle puppies, but not mature dogs, was also quite different compared to data published in younger adult dogs.