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Overexpression of renin in the collecting duct causes hypertension
Author(s) -
Ramkumar Nirupama,
Ying Jian,
Stuart Deborah,
Kohan Donald E
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.909.4
Subject(s) - renin–angiotensin system , plasma renin activity , medicine , endocrinology , kidney , messenger rna , biology , excretion , microbiology and biotechnology , gene , chemistry , blood pressure , biochemistry
The role of collecting duct (CD)‐derived renin in regulating arterial pressure (BP) is unknown. To examine proof of concept, gene targeting was used to obtain mice with renin overexpression in the CD. Mice were generated in which the sequence: loxP ‐ PGK promoter‐Neo R ‐ transcriptional stop sequence – loxP ‐ Ren1 cDNA – bovine growth hormone polyA was knocked in to the ROSA26 locus. These mice were crossed with mice transgenic for aquaporin 2 AQP2) promoter‐Cre recombinase, resulting in excision of the PGK‐Neo‐Stop and CD‐specific overexpression of renin (CD renin mice). Mice heterozygous for the knock‐in allele and AQP2‐Cre were studied. BP was recorded by telemetry and plasma and urine were collected in metabolic cages on normal, high and low Na diets. DNA recombination and PCR for ROSA‐renin mRNA confirmed kidney‐specific expression. Medullary renin mRNA was increased 5‐fold and urinary renin excretion was increased 2.5‐fold in CD renin mice. CD renin mice had salt‐sensitive hypertension that was most apparent on a high Na diet (mean BP 105 ± 2 mmHg vs. 95 ± 2 mmHg in wild type). Plasma renin concentration (PRC) was reduced by ~50% and ~80% in CD renin mice on a normal or high Na diet, respectively, as compared to WT animals. There were no differences in BP or PRC between CD renin and WT mice fed a low Na diet. These findings indicate that CD‐derived renin has the potential to modulate BP and that this effect is due to local, and not systemic, renin activity.