Mice with targeted deletion of NBCe2 are hypertensive

Abstract

Single nucleotide polymorphisms in the electrogenic Na+ HCO3− cotransporter NBCe2 gene are associated with human hypertension. NBCe2 mRNA has been shown in many tissues including brain and kidney, all though the function of the transporter in these tissues remains unknown. The aim of this study was to determine whether deletion of NBCe2 causes hypertension in mice and to investigate whether the hypertension is salt sensitive. A full NBCe2 knockout mouse (NBCe2 ko) was generated and validated by quantitative PCR analysis of kidney and brain tissue. Tail‐cuff blood pressure measurements over a 10 day period revealed that the NBCe2 ko mice were hypertensive compared to wildtype (wt) mice (MAP (mmHg): 117±2 in NBCe2 ko mice, 83±−2 in wt ). Telemetry measurements confirmed this difference in blood pressure. Preliminary data suggest that 4% dietary Na+lead to an increase in blood pressure in both genotypes, while 0.02% Na+ diet decreased blood pressure in both genotypes. In conclusion, deletion of NBCe2 in mice causes increased systemic blood pressure. The hypertension is augmented by increasing dietary sodium, but is not abolished by low sodium diet. The mechanism causing the phenotype requires further investigation. Supported by the Lundbeck Foundation.