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Decreased klotho expression in early aldosterone‐induced hypertension
Author(s) -
Takenaka Tsuneo,
Inoue Tsutomu,
Okada Hirokazu,
Miyazaki Takashi,
Suzuki Hiromichi
Publication year - 2010
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.24.1_supplement.lb698
Subject(s) - klotho , medicine , endocrinology , aldosterone , mineralocorticoid receptor , mineralocorticoid , blood pressure , nephron , kidney , excretion , creatinine , chemistry
Aldosterone activates mineralocorticoid receptor in distal nephron. Klotho is expressed in distal nephron, and suppresses oxidative stress. However, the effects of aldosterone on klotho expression have not adequately examined. In the present study, the expression of klotho was assessed in 4 groups of rats; Wistar rats as a control (C), aldosterone‐infused (0.75 μg/hr SQ) rats (A), rats fed high (6%) salt diet (S), and rats loaded with both aldosterone and salt (A+S). Initially, left nephrectomy was performed in all rats. After a week of recovery, aldosterone and/or salt load was started. A week later, rats were killed with over‐anesthesia, and harvested right kidney for analysis. Mean blood pressure in A+S group (111±6 mmHg, n=5, p<0.05) was higher than C group (97±3 mmHg, n=5). Significant changes in blood pressure were seen in neither A nor S group. In addition, creatinine clearance and albumin excretion were similar among 4 groups. However, 8‐epi‐prostaglandin F2α excretion was markedly increased in A+S group (13±3 ng/24hr, p<0.01), compared to C group (5±1 ng/24hr). RT‐PCR and immunoblot using monoclonal antibody against klotho (KM2076) revealed that compared to C group, renal klotho expression was impaired in A+S group, assessed by mRNA (45±8 %, p<0.05) and protein level (50±11 %, p<0.05). Group A and S did not show significant changes in klotho expression. Our data indicated that blood pressure was mildly elevated in early aldosterone salt‐induced hypertension. The present findings provided the evidence that klotho expression was reduced before developing overt nephropathy. Our results suggest that a reduced klotho expression may accelerate oxidative stress in aldosterone salt‐induced hypertension.