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Salt‐inducible kinase 1 knockout mice show a salt‐retaining phenotype and salt‐sensitive hypertension (1136.5)
Author(s) -
Pinho Maria,
Pires Nuno,
Igreja Bruno,
Brion Laura,
Bertorello Alejandro,
SoaresdaSilva Patricio
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1136.5
Subject(s) - endocrinology , medicine , homeostasis , blood pressure , pseudohypoaldosteronism , knockout mouse , kidney , aldosterone , chemistry , biology , receptor
Essential hypertension is associated with alterations of sodium homeostasis, which promote abnormal accumulation of water in the intravascular compartment leading to blood pressure elevations. Salt‐inducible kinase 1 (SIK1) belongs to the AMPK family and a single nucleotide polymorphism within the human SIK1 gene is associated with hypertension [lower SIK1 activity is associated with higher blood pressure (HBP)]. SIK1 network mediates sodium‐dependent signals that modulate the activity of the Na+,K+‐ATPase. We aimed to study the role of SIK1 in cardiovascular and renal homeostasis using SIK1 knockout (KO) mice. No differences in BP were observed between sik1‐/‐ and sik1+/+ mice under 0.3% NaCl diet; however, the sik1‐/‐ mice challenged with an acute or chronic 8% NaCl diet showed increased SBP. We found that under an 8% NaCl diet, Na+, K+ and Cl‐ excretion was significantly lower in sik1‐/‐ mice compared with wild type mice, despite similar plasma aldosterone levels. The impaired ability of sik1‐/‐ to eliminate Na+ under 8% NaCl diet was accompanied by hyperkalemia. Signs of fibrosis were observed in sik1‐/‐ mice kidneys (increased glomerular and interstitial collagen deposition) vs. wild type mice. At the molecular level, this phenotype was accompanied by an increased in collagen α1 and α4 and MMP9 mRNA, and a reduction in E‐cadherin and nephrin mRNA levels. These results indicate that the presence of SIK1 is necessary to prevent the development of hypertension. Grant Funding Source : Supported by FCT (PIC/IC/83204/2007).