Abnormal regulation of proximal tubule renin mRNA in the Dahl/Rapp salt- sensitive rat

Julia E. Tank, Orson W. Moe, William L. Henrich

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Abstract

Background. The precise pathogenesis of salt-sensitive hypertension in the Dahl rat is unknown. Abnormalities in renal hemodynamics and NaCl handling have been implicated, and may relate to changes in the activity of the intrarenal renin-angiotensin system. Methods. Circulating, juxtaglomerular and intrarenal (glomerular and proximal tubular) renin were studied in Dahl/Rapp salt-sensitive and salt-resistant rats fed with a normal (0.5%) or high (4%) NaCl diet. Circulating and juxtaglomerular renin were assessed by measurement of plasma renin activity and renin secretory rates. Glomerular and proximal tubular renin mRNA were assessed by microdissection and quantitative competitive RT-PCR. Results. Circulating and juxtaglomerular renin were suppressed by high dietary NaCl in salt-sensitive rats (plasma renin activity, 0.5%, 10.9 ± 0.7 vs. 4%, 7.9 ± 0.3 ng/ml/hr, P < 0.05; renin secretory rate, 0.5% 220 ± 32 vs. 4%, 58 ± 5 ng/mg/hr, P < 0.05). Glomerular renin mRNA was also suppressed by the higher salt diet in salt- sensitive animals (0.5%, 411 ± 84 vs. 4%, 67 ± 22 x 103 copies/glomerulus, P < 0.05). In contrast, proximal tubular renin was not suppressed by a high NaCl diet in salt-sensitive animals (0.5%, 13.9 ± 2.7 vs. 4%, 12.1 ± 3.6 x 103 copies/mm tubule, P = NS), but was suppressed in salt-resistant rats (0.5%, 9.5 ± 2.8 vs. 4%, 3.2 ± 1.2 x 103 copies/mm, P < 0.05). Conclusions. Failure to suppress proximal tubular renin in response to high dietary NaCl may result in increased local generation of angiotensin II and enhanced proximal tubular NaCl absorption, and thereby contribute to the generation of salt sensitive hypertension.

Original languageEnglish (US)
Pages (from-to)1608-1616
Number of pages9
JournalKidney International
Volume54
Issue number5
DOIs
Publication statusPublished - 1998

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Keywords

  • Angiotensin II
  • Glomerulus
  • Hypertension
  • Renin-angiotensin system
  • Sodium chloride

ASJC Scopus subject areas

  • Nephrology

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