Premium
Renin knock out modulates sodium reabsorption in the Dahl salt‐sensitive rats
Author(s) -
Pavlov Tengis S,
Levchenko Vladislav,
Ilatovskaya Daria V,
MorenoQuinn Carol,
Staruschenko Alexander
Publication year - 2013
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.27.1_supplement.909.6
Subject(s) - aldosterone , epithelial sodium channel , medicine , endocrinology , renin–angiotensin system , plasma renin activity , reabsorption , chemistry , homeostasis , blood pressure , sodium , kidney , renal sodium reabsorption , nephron , biology , organic chemistry
Dahl salt‐sensitive (SS) rats fed a high salt diet exhibit increased blood pressure and renal damage. We have shown recently that ENaC expression and activity were significantly enhanced in SS rats fed a high salt diet. The renin‐angiotensin‐aldosterone system (RAAS) regulates blood pressure and water electrolyte homeostasis, and renin is a critical component of this system. Ren −/− rats were used to further investigate the role of the renin and RAAS in regulation of sodium transport in salt‐sensitive hypertension. Knock out rats were created using zinc‐finger nucleases designed to target the renin gene in the SS rat. As it has been shown previously, Ren −/− rats have lower body weight and blood pressure whereas no difference is observed in plasma and urine Na + concentration compared to WT littermates. Here we demonstrate that aldosterone level is significantly lower in Ren −/− rats compared to WT littermates. Aldosterone level is also suppressed in SS rats fed high salt diet compared to animals fed low salt. Single‐channel patch clamp analysis of the freshly isolated collecting ducts revealed decreased ENaC activity in Ren −/− rats. Expression of ENaC subunits was also assessed by immunohistochemistry and Western blotting. We conclude that renin knock out causes low blood pressure, decrease in aldosterone level and suppression of ENaC activity in the aldosterone‐sensitive distal nephron. Supported by AHA, ADA and NIH.