Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension
| Autor: | Reginaldo Nassar Ferreira, D. Graziani, Gustavo Rodrigues Pedrino, Rodrigo Mello Gomes, Michelle Mendanha Mendonça, Elder Sales da Silva, Patrícia Maria Ferreira, Amanda de Sá Martins de Bessa, Erika Fernandes, Lilian Fernanda Pacheco, Carolina Nobre Ribeiro Pontes, Carlos Henrique de Castro, Larissa Cristina dos Santos Ribeiro, Lara Marques Naves, Carlos Henrique Xavier |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Indoles Renal cortex Growth hormone secretagogue receptor Hemodynamics Renal function Down-Regulation 030209 endocrinology & metabolism Kidney Kidney Function Tests Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine medicine.artery Rats Inbred SHR medicine Animals Spiro Compounds Renal artery Rats Wistar Receptors Ghrelin Molecular Biology business.industry Sodium Imidazoles Brain Neurogenic hypertension Ghrelin Rats Disease Models Animal 030104 developmental biology medicine.anatomical_structure Hypertension Potassium business hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular and cellular endocrinology. 518 |
| ISSN: | 1872-8057 |
| Popis: | Ghrelin is a peptide hormone whose effects are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), mainly expressed in the brain but also in kidneys. The hypothesis herein raised is that GHS-R1a would be player in the renal contribution to the neurogenic hypertension pathophysiology. To investigate GHS-R1a role on renal function and hemodynamics, we used Wistar (WT) and spontaneously hypertensive rats (SHR). First, we assessed the effect of systemically injected vehicle, ghrelin, GHS-R1a antagonist PF04628935, ghrelin plus PF04628935 or GHS-R1a synthetic agonist MK-677 in WT and SHR rats housed in metabolic cages (24 h). Blood and urine samples were also analyzed. Then, we assessed the GHS-R1a contribution to the control of renal vasomotion and hemodynamics in WT and SHR. Finally, we assessed the GHS-R1a levels in brain areas, aorta, renal artery, renal cortex and medulla of WT and SHR rats using western blot. We found that ghrelin and MK-677 changed osmolarity parameters of SHR, in a GHS-R1a-dependent manner. GHS-R1a antagonism reduced the urinary Na+ and K+ and creatinine clearance in WT but not in SHR. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a protein levels were decreased in the kidney and brain areas of SHR when compared to WT. Therefore, GHS-R1a role in the control of renal function and hemodynamics during neurogenic hypertension seem to be different, and this may be related to brain and kidney GHS-R1a downregulation. |
| Databáze: | OpenAIRE |
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