Angiotensin subtype-2 receptors inhibit renin biosynthesis and angiotensin II formation

Helmy M. Siragy, Chun Xue, Peter Abadir, Robert M. Carey

Research output: Contribution to journalArticlepeer-review

Abstract

Renin is regulated by angiotensin subtype 1 (AT1) receptor, but it is unknown whether angiotensin subtype 2 (AT2) receptor contributes to this regulation. We hypothesized that AT2 receptors inhibit angiotensin II (Ang II) through inhibition of renin biosynthesis. We monitored changes in renal Ang II, renin mRNA and protein expression, and plasma renin concentration (PRC) in response to renal cortical administration of the AT1 receptor blocker valsartan or the AT2 receptor blocker PD 123319 (PD) in conscious rats administered low sodium intake (LS). Renal interstitial Ang II increased by 47-fold in response to LS and increased further in response to valsartan or PD by 67-fold and 61-fold from normal sodium diet (NS) and by ≈41% and 29% from LS, respectively. Renin mRNA increased 63% during LS, and either valsartan or PD increased it further by 600% and 250% from NS and 538% and 187% from LS, respectively. Similarly, renal renin content and PRC increased in response to LS and increased further in response to combined LS and valsartan or PD administration. Immunostaining for renal renin protein demonstrated an increase in its expression in juxtaglomular and tubular cells during LS and increased further during AT1 or AT2 receptor blockade. These data demonstrate for the first time to our knowledge that AT2 receptors regulate the renin-angiotensin system activity via inhibition of renin synthesis.

Original languageEnglish (US)
Pages (from-to)133-137
Number of pages5
JournalHypertension
Volume45
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Keywords

  • Angiotensin
  • Kidney
  • Receptors, angiotensin
  • Renin

ASJC Scopus subject areas

  • Internal Medicine

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