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Enhancement of renin and prorenin receptor in collecting duct of Cyp1a1-Ren2 rats may contribute to development and progression of malignant hypertension.

Abstract
To determine whether in the transgenic rat model [TGR(Cyp1a1Ren2)] with inducible ANG II-dependent malignant hypertension changes in the activation of intrarenal renin-angiotensin system may contribute to the pathogenesis of hypertension, we examined the gene expression of angiotensinogen (AGT) in renal cortical tissues and renin and prorenin receptor [(P)RR] in the collecting duct (CD) of the kidneys from Cyp1a1Ren2 rats (n = 6) fed a normal diet containing 0.3% indole-3-carbinol (I3C) for 10 days and noninduced rats maintained on a normal diet (0.6% NaCl diet; n = 6). Rats induced with I3C developed malignant hypertension and exhibited alterations in the expression of renin and (P)RR expressed by the CD cells. In the renal medullary tissues of the Cyp1a1Ren2 transgenic rats with malignant hypertension, renin protein levels in CD cells were associated with maintained renin content and lack of suppression of the endogenous Ren1c gene expression. Furthermore, these tissues exhibited increased levels of (P)RR transcript, as well as of the protein levels of the soluble form of this receptor, the s(P)RR. Intriguingly, although previous findings demonstrated that urinary AGT excretion is augmented in Cyp1a1Ren2 transgenic rats with malignant hypertension, in the present study we did not find changes in the gene expression of AGT in renal cortical tissues of these rats. The data suggest that upregulation of renin and the s(P)RR in the CD, especially in the renal medullary tissues of Cyp1a1Ren2 transgenic rats with malignant hypertension, along with the previously demonstrated increased availability of AGT in the urine of these rats, may constitute a leading mechanism to explain elevated formation of kidney ANG II levels in this model of ANG II-dependent hypertension.
AuthorsMinolfa C Prieto, Dustyn E Williams, Liu Liu, Kimberly L Kavanagh, John J Mullins, Kenneth D Mitchell
JournalAmerican journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 300 Issue 2 Pg. F581-8 (Feb 2011) ISSN: 1522-1466 [Electronic] United States
PMID21068087 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Indoles
  • Receptors, Cell Surface
  • Ren2 protein, rat
  • Angiotensinogen
  • Angiotensin II
  • indole-3-carbinol
  • Cytochrome P-450 CYP1A1
  • Renin
  • Prorenin Receptor
Topics
  • Angiotensin II (metabolism)
  • Angiotensinogen (metabolism)
  • Animals
  • Cytochrome P-450 CYP1A1 (genetics, metabolism)
  • Gene Expression (drug effects)
  • Hypertension, Malignant (metabolism)
  • Indoles (pharmacology)
  • Kidney Cortex (drug effects, metabolism)
  • Kidney Medulla (metabolism, physiopathology)
  • Kidney Tubules, Collecting (drug effects, metabolism)
  • Male
  • Rats
  • Rats, Transgenic
  • Receptors, Cell Surface (metabolism)
  • Renin (genetics, metabolism)
  • Renin-Angiotensin System (drug effects, physiology)
  • Prorenin Receptor

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