Abstract P203: Renal Localization of Salt Inducible Kinase-1 and Its Regulation in Doca/salt Hypertensive Rats
| Autor: | Fernanda M. Ferrão, Minolfa C. Prieto, Sabrina R. Gonsalez, Lucienne S. Lara |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Hypertension. 68 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | In immortalized and primary cultured renal cells, SIK-1 is the intracellular Na + sensor enabling cells to enhance (Na + +K + )ATPase (NKA) activity without promoting cell swelling. In the present study, we aimed to: (1) Localize SIK-1 along the nephron; (2) To determine the effects of high salt (HS) diet and hypertension (HTN) on SIK-1 expression and activity; and (3) To examine the SIK-related impact on NKA. Adult male Wistar rats (N=60; N=15/group) underwent to unilateral nephrectomy and divided in four groups: 1) Control (CTRL); 2) CTRL/Salt (4% NaCl); 3) Deoxycorticosterone acetate (DOCA; sc 8 mg/kg; twice a week); and 4) DOCA/Salt. After 4 weeks, systolic blood pressures (SBP) were measured by tail-cuff and then, rats were maintained in metabolic cages during 24 h for urine collections. At euthanasia, remaining kidney was removed for kidney index, histological analyses and renal cortex homogenate preparation. Regardless, salt intake, CTRL rats presented normal SBP, kidney histology, and glomerular filtration rate (GFR). However, CTRL/Salt rats exhibited augmented fractional Na + excretion (FENa), BUN, and proteinuria. DOCA/Salt rats presented exacerbated SBP and FENa, marked kidney injury, and decreased GFR. In all groups, SIK-1 immunofluorescence was localized in mesangial cells, thick ascending limb, and principal cells. In CTRL rats, high-salt diet increased 40% SIK-1 protein content and 4-fold SIK activity. NKA activity increased from 101±5 to 211±47 nmol Piхmg -1 хmin -1 in CTRL/Salt rats, but SIK inhibition brought back NKA to control values. In contrast, in DOCA/Salt rats, SIK-1 protein content did not change, SIK activity increased 2-fold, and NKA activity decreased from 77±5 to 47±6 nmol Piхmg -1 хmin -1 . In these rats, SIK inhibition significantly decreased NKA activity. Our data indicate that SIK-1 induces Na + reabsorption by increasing NKA activity but during DOCA salt-sensitive hypertension, there is SIK-1 dysregulation, which contributes in part to kidney injury. |
| Databáze: | OpenAIRE |
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