TY - JOUR
T1 - Renal sodium transport in renin-deficient Dahl salt-sensitive rats
AU - Pavlov, Tengis S.
AU - Levchenko, Vladislav
AU - Ilatovskaya, Daria V.
AU - Moreno, Carol
AU - Staruschenko, Alexander
N1 - Publisher Copyright:
©The Author(s) 2016.
PY - 2016
Y1 - 2016
N2 - Objective: The Dahl salt-sensitive rat is a well-established model of salt-sensitive hypertension. The goal of this study was to assess the expression and activity of renal sodium channels and transporters in the renin-deficient salt-sensitive rat. Methods: Renin knockout (Ren-/-) rats created on the salt-sensitive rat background were used to investigate the role of renin in the regulation of ion transport in salt-sensitive hypertension. Western blotting and patch-clamp analyses were utilized to assess the expression level and activity of Na+ transporters. Results: It has been described previously that Ren-/- rats exhibit severe kidney underdevelopment, polyuria, and lower body weight and blood pressure compared to their wild-type littermates. Here we found that renin deficiency led to decreased expression of sodium-hydrogen antiporter (NHE3), the Na+/H+ exchanger involved in Na+ absorption in the proximal tubules, but did not affect the expression of Na-K-Cl cotransporter (NKCC2), the main transporter in the loop of Henle. In the distal nephron, the expression of sodium chloride cotransporter (NCC) was lower in Ren-/- rats. Single-channel patch clamp analysis detected decreased ENaC activity in Ren-/- rats which was mediated via changes in the channel open probability. Conclusion: These data illustrate that renin deficiency leads to significant dysregulation of ion transporters.
AB - Objective: The Dahl salt-sensitive rat is a well-established model of salt-sensitive hypertension. The goal of this study was to assess the expression and activity of renal sodium channels and transporters in the renin-deficient salt-sensitive rat. Methods: Renin knockout (Ren-/-) rats created on the salt-sensitive rat background were used to investigate the role of renin in the regulation of ion transport in salt-sensitive hypertension. Western blotting and patch-clamp analyses were utilized to assess the expression level and activity of Na+ transporters. Results: It has been described previously that Ren-/- rats exhibit severe kidney underdevelopment, polyuria, and lower body weight and blood pressure compared to their wild-type littermates. Here we found that renin deficiency led to decreased expression of sodium-hydrogen antiporter (NHE3), the Na+/H+ exchanger involved in Na+ absorption in the proximal tubules, but did not affect the expression of Na-K-Cl cotransporter (NKCC2), the main transporter in the loop of Henle. In the distal nephron, the expression of sodium chloride cotransporter (NCC) was lower in Ren-/- rats. Single-channel patch clamp analysis detected decreased ENaC activity in Ren-/- rats which was mediated via changes in the channel open probability. Conclusion: These data illustrate that renin deficiency leads to significant dysregulation of ion transporters.
KW - Aldosterone-sensitive distal nephron
KW - Epithelial sodium channel
KW - Na-K-Cl cotransporter
KW - Renin-angiotensin-aldosterone system
KW - Sodium chloride cotransporter
KW - Sodium-hydrogen antiporter
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U2 - 10.1177/1470320316653858
DO - 10.1177/1470320316653858
M3 - Article
C2 - 27443990
AN - SCOPUS:84983341158
SN - 1470-3203
VL - 17
JO - JRAAS - Journal of the Renin-Angiotensin-Aldosterone System
JF - JRAAS - Journal of the Renin-Angiotensin-Aldosterone System
IS - 3
ER -