Published online before print September 10, 2007, doi: 10.1161/HYPERTENSIONAHA.107.096891
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(Hypertension. 2007;50:933.)
© 2007 American Heart Association, Inc.
Original Articles |
Renin Enhancer Is Crucial for Full Response in Renin Expression to an In Vivo Stimulus
From the Basic & Clinical Genomics Laboratory (M.A.M., C.G., B.J.M.) and Discipline of Anatomy & Histology (F.J.L.), School of Medical Sciences and Bosch Institute, The University of Sydney, New South Wales, Australia; and The Wellcome Trust Sanger Institute (D.J.A.), Wellcome Trust Genome Campus, Hinxton, Cambs, CB10 1SA, UK.
Correspondence to Brian J. Morris, DSc, Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, Building F13, University of Sydney, NSW 2006, Australia. E-mail brianm{at}medsci.usyd.edu.au
We showed recently that deletion of a strong enhancer located 2.7 kb upstream of the renin gene in mice produces a strain with mild hypotension and salt-sensitivity. Here we set out to compare responses in renin expression in kidney and extrarenal tissues in these "REKO" mice. REKO and wild-type mice were placed on a low NaCl/enalapril regimen for 1 week, and then Ren-1c mRNA and renin enzyme activities were measured in tissues and plasma. In untreated REKO mice, renin and Ren-1c mRNA were reduced significantly in kidney, submandibular gland, adrenal, heart, and brain. In situ hybridization indicated a marked reduction in Ren-1c mRNA in juxtaglomerular cells and granular ducts of submandibular gland. After the chronic stimulus response in renal Ren-1c mRNA in REKO mice was blunted by 54% compared with wild-type mice, and was accompanied by almost complete exhaustion of renin stores. Response in plasma renin was blunted by 47%, this being mirrored in heart (54% decline), in which renin is derived mostly from the bloodstream. In adrenal a 55% reduction was seen. These data are consistent with inability of REKO mice to adequately replenish renal renin stores during chronic stimulation of renin secretion. In conclusion, the renin enhancer is critical for replenishment of renin stores and response in renin to a chronic in vivo stimulus.
Key Words: renin gene expression • enhancer • knockout mouse • low sodium diet • angiotensin converting enzyme inhibitor • renin mRNA • renin enzymatic activity • kidney • extrarenal renin expression
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