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Inactivation of Hv1 proton channels is not responsible for bicarbonate‐mediated reductions in tubular cast formation in Dahl salt‐sensitive rats
Author(s) -
Ray Sarah,
Ocasio Hiram,
Sun Jingping,
O'Connor Paul M
Publication year - 2017
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.31.1_supplement.855.9
Subject(s) - bicarbonate , endocrinology , medicine , chemistry , blood pressure , proteinuria , kidney
We have shown that oral bicarbonate promotes a marked reduction in tubular cast formation and fibrosis in the Dahl salt‐sensitive (SS) rat model when fed a high salt diet, independent of arterial blood pressure, glomerular sclerosis, and proteinuria. Rats lacking the voltage‐gated proton channel (Hv1), which is highly expressed in mTAL, denoted a similar phenotype. In the current study, we examined whether bicarbonate intake protected from cast formation in the Dahl SS rat model by inactivation of the voltage‐gated Hv1 proton channel. Wild‐type Dahl SS (WT) and Hv1 knock‐out (KO) Dahl SS rats were treated with either vehicle (0.1M NaCl; n=9) or bicarbonate (0.1M NaHCO 3 ; n=11) in drinking water for the length of the study. Following a 4 day baseline period in which both groups were fed a 0.4% NaCl diet (Dyets AIN76A), rats were placed on an 8% NaCl diet for 14 days. Urine was collected at day 4 of baseline, day 7, and day 14 high salt; telemetry was used to measure blood pressure. On day 14, rats were anesthetized, and the right kidney taken for histology. Mean arterial pressure (mmHg) showed no difference between the WT and KO groups regardless of vehicle or bicarbonate treatment. Tubular casts were significantly decreased (p STRAIN =0.008) in KO rats when compared to WT. Importantly, bicarbonate treatment had an additive effect, further decreasing tubular cast formation and by a similar magnitude in both KO and WT rats (P TREATMENT =0.02; P TREATMENT*STRAIN =N.S). In conclusion, bicarbonate‐induced inactivation of Hv1 proton channels does not mediate the reduction of cast formation in Dahl SS rats. Further investigation will be required to determine whether a common downstream mechanism is responsible for limiting tubular cast formation in the absence of blood pressure changes or glomerular injury in bicarbonate treated and Hv1 −/− Dahl SS rats. Support or Funding Information The authors would like to acknowledge funding from the National Institute of Health: NIDDK R01099548