Abstract 318: The Role of PKC-alpha in NCC-Mediated Hypertension
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Abstract
The sodium-chloride cotransporter (NCC) is an essential regulator of sodium transport in the distal convoluted tubule (DCT); functional aberrations will lead to dysregulation of blood pressure. Although this role is well-accepted, the mechanisms accounting for increased distal nephron sodium reabsorption is not completely understood. Previously published data from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study has demonstrated that a polymorphism in PKC-alpha may lead to an increased sensitivity to thiazide diuretics. To investigate whether PKC-alpha may be altering blood pressure via NCC, PKC-alpha KO (PKC KO) and PKC Control (Ctl) mice were used to measure blood pressure via radiotelemetry after normal and high salt (HS, 4%) dietary manipulations and Western blot analysis performed using kidney lysates. Using radiotelemetry (DSI) measurements obtained over an 18 hour ‘active’ time period, we report a significant increase in mean arterial pressure (MAP) in the PKC KO mice as compared to control (123.2±1.1 mmHg vs. 102.0±0.77 mmHg, p<0.001). With HS feeding, MAP increased in both groups; in addition MAP remained significantly higher in the PKC KO mice as compared to the Ctl after 21 days (139.5±0.3 mmHg vs. 124.7±1.1 mmHg, p<0.01). To determine a possible mechanism for this phenomenon, whole kidney lysate was used to assay for total NCC protein. Total NCC protein was almost 3 fold higher in the PKC KO mice as compared to Ctl (in arbitrary units, 208±16 vs. 61±30, p<0.01). Herein we report that lack of PKC-alpha leads to an increase in MAP, which may be accounted for by increased total NCC expression and a subsequent increase in distal nephron reabsorption. We believe that PKC-alpha may be negative regulator of NCC protein expression, and that aberrations in this pathway will lead to hypertension.
Author Disclosures: B.M. Wynne: None. P. Molina: None. J.D. Klein: None. R.S. Hoover: None.
- © 2014 by American Heart Association, Inc.
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- Abstract 318: The Role of PKC-alpha in NCC-Mediated HypertensionBrandi M Wynne, Patrick Molina, Janet D Klein and Robert S HooverHypertension. 2014;64:A318, originally published February 5, 2015
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