AT1 Receptor Blockade Prevents the Increase in Blood Pressure and the Augmentation of Intrarenal ANG II Levels in Hypertensive Cyp1a1-Ren2 Transgenic Rats Fed With a High-Salt Diet

Dustyn E. Williams, Minolfa C. Prieto, John J. Mullins, L. Gabriel Navar, Kenneth D. Mitchell

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: This study was performed to determine the effects of high-salt diet on the magnitude of the increases in systolic blood pressure (SBP) and kidney tissue angiotensin (ANG) II levels that occur after induction of ANG II-dependent malignant hypertension in Cyp1a1-Ren2 transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)]. Methods: Cyp1a1Ren2 rats (n = 6) were fed a normal diet containing 0.3% indole-3-carbinol (I3C) for 10 days to induce ANG II-dependent malignant hypertension. Results: Rats induced with I3C exhibited increases in SBP and elevations of ANG II levels in kidney cortex and medulla. In a second group of rats (n = 6), high-salt intake alone did not alter basal SBP; however, subsequent dietary administration of 0.3% I3C during continued high-salt intake elicited a substantially greater increase in SBP than observed in rats fed a normal salt diet. ANG II levels in kidney cortex and medulla of rats induced with I3C and fed a high-salt diet were elevated similarly to those in rats induced with I3C alone. Chronic administration of the AT 1 receptor antagonist, losartan (100 mg/L in drinking water, n = 6), markedly attenuated the I3C-induced increase in SBP and prevented the augmentation of ANG II levels in kidney cortex and medulla in rats induced with I3C and maintained on a high-salt diet. Conclusions: Activation of AT 1 receptors contributes to the augmented blood pressure and elevated kidney tissue ANG II levels that occur in Cyp1a1-Ren2 transgenic rats with malignant hypertension maintained on a high-salt diet.

Original languageEnglish
Pages (from-to)356-361
Number of pages6
JournalAmerican Journal of the Medical Sciences
Volume339
Issue number4
DOIs
Publication statusPublished - Apr 2010

Keywords

  • kidney
  • renin-angiotensin system
  • radioimmunoassay
  • malignant hypertension
  • sodium-dependent

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