Attenuated diuresis and natriuresis in response to glucagon-like peptide-1 in hypertensive rats are associated with lower expression of the glucagon-like peptide-1 receptor in the renal vasculature
| Autor: | Fernanda A. Savignano, Luciene Cristina Gastalho Campos, Renato O. Crajoinas, Antonio Carlos Seguro, Bruna Piccolo Muniz Pacheco, Adriana C. C. Girardi, Maria Heloisa Massola Shimizu |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty medicine.medical_treatment Natriuresis Diuresis Incretin Renal function Vasodilation 030204 cardiovascular system & hematology Glucagon-Like Peptide-1 Receptor 03 medical and health sciences Renal Artery 0302 clinical medicine Glucagon-Like Peptide 1 Internal medicine medicine.artery Cyclic AMP medicine Animals Renal artery Pharmacology business.industry digestive oral and skin physiology Glucagon-like peptide-1 Rats 030104 developmental biology Endocrinology Gene Expression Regulation Hypertension Diuretic business hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | European Journal of Pharmacology. 811:38-47 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2017.05.054 |
| Popis: | Accumulating evidence from clinical and experimental studies indicates that the incretin glucagon-like peptide-1 (GLP-1) elicits blood-pressure lowering effects via its diuretic, natriuretic and vasodilatory properties. The present study investigated whether acute infusion of GLP-1 induces diuresis and natriuresis in spontaneously hypertensive rats (SHRs). Additionally, we examined whether GLP-1 influences the vascular reactivity of the renal arteries of normotensive and hypertensive rats and elucidated the underlying mechanisms. We found that the increase in urinary output and urinary sodium excretion in response to systemic infusion of GLP-1 for 30min in SHRs was much less pronounced than in normotensive rats. The diuretic and natriuretic actions of GLP-1 in normotensive rats were accompanied by increases in GFR and RBF and a reduction in RVR through activation of the cAMP signaling pathway. However, no changes in renal hemodynamics were observed in SHRs. Similarly, GLP-1 induced an endothelium-independent relaxation effect in the renal arteries of normotensive rats, whereas the renal vasculature of SHRs was unresponsive to this vasodilator. The absence of a GLP-1-induced renal artery vasodilator effect in SHRs was associated with lower expression of the GLP-1 receptor, blunted GLP-1-induced increases in cAMP production and higher activity and expression of the GLP-1 inactivating enzyme dipeptidyl peptidase IV relative to the renal arteries of normotensive rats. Collectively, these results demonstrate that the renal acute responses to GLP-1 are attenuated in SHRs. Thus, chronic treatment with incretin-based agents may rely upon the upregulation of GLP-1/GLP-1 receptor signaling in the kidneys of hypertensive patients and experimental models. |
| Databáze: | OpenAIRE |
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