Sodium butyrate ameliorates deoxycorticosterone acetate/salt-induced hypertension and renal damage by inhibiting the MR/SGK1 pathway
Autor: | Yeyan Zhu, Chunying Wu, Lei Wang, Mokan Deng, Qing Zhu, Yuting Liu, Cailin Huang, Linlin Zhang, Chen Zhida |
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Rok vydání: | 2019 |
Předmět: |
Male
medicine.medical_specialty Physiology Sodium chemistry.chemical_element Blood Pressure 030204 cardiovascular system & hematology Acetates Protein Serine-Threonine Kinases Sodium Chloride urologic and male genital diseases Kidney Immediate-Early Proteins Excretion Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Desoxycorticosterone Acetate 0302 clinical medicine Mineralocorticoid receptor Oral administration Internal medicine Renin–angiotensin system Internal Medicine medicine Renal medulla Animals 030212 general & internal medicine Sodium Chloride Dietary urogenital system Sodium butyrate Rats Endocrinology medicine.anatomical_structure Receptors Mineralocorticoid chemistry Hypertension SGK1 Butyric Acid Kidney Diseases Cardiology and Cardiovascular Medicine Signal Transduction |
Zdroj: | Hypertension research : official journal of the Japanese Society of Hypertension. 44(2) |
ISSN: | 1348-4214 |
Popis: | Our recent work demonstrates that infusion of sodium butyrate (NaBu) into the renal medulla blunts angiotensin II-induced hypertension and improves renal injury. The present study aimed to test whether oral administration of NaBu attenuates salt-sensitive hypertension in deoxycorticosterone acetate (DOCA)/salt-treated rats. Uninephrectomized male Sprague-Dawley (SD) rats were treated with DOCA pellets (150 mg/rat) plus 1% NaCl drinking water for 2 weeks. Animals received oral administration of NaBu (1 g/kg) or vehicle once per day. Our results showed that NaBu administration significantly attenuated DOCA/salt-increased mean arterial pressure from 156 ± 4 mmHg to 136 ± 1 mmHg. DOCA/salt treatment markedly enhanced renal damage as indicated by an increased ratio of kidney weight/body weight, elevated urinary albumin, extensive fibrosis, and inflammation, whereas kidneys from NaBu-treated rats exhibited a significant reduction in these renal damage responses. Compared to the DOCA/salt group, the DOCA/salt-NaBu group had ~30% less salt water intake and decreased Na+ and Cl- excretion in urine but no alteration in 24-h urine excretion. Mechanistically, NaBu inhibited the protein levels of several sodium transporters stimulated by DOCA/salt in vivo, such as βENaC, γENaC, NCC, and NKCC-2. Further examination showed that NaBu downregulated the expression of mineralocorticoid receptor (MR) and serum and glucocorticoid-dependent protein kinase 1 (SGK1) in DOCA/salt-treated rats or aldosterone-treated human renal tubular duct epithelial cells. These results provide evidence that NaBu may attenuate DOCA/salt-induced hypertension and renal damage by inhibiting the MR/SGK1 pathway. |
Databáze: | OpenAIRE |
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