Angiotensin II type 2 receptor inhibits prorenin processing in juxtaglomerular cells

Atsuhiro Ichihara, Matsuhiko Hayashi, Nobuhisa Hirota, Hirokazu Okada, Yukako Koura, Yuko Tada, Yuki Kaneshiro, Hirohiko Tsuganezawa, Takao Saruta

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21 Citations (Scopus)

Abstract

Long-term treatment with an angiotensin II type 1 receptor blocker (ARB) has been shown to decrease the plasma renin activity (PRA) of hypertensive patients, whereas PRA remains elevated during angiotensin-converting enzyme inhibitor (ACEI) treatment. In the present study, we used rat juxtaglomerular (JG) cells to elucidate the mechanism(s) involved in the differential regulation of PRA between ARB and ACEI treatment. Addition of 100 nmol/l angiotensinogen (Aogen) to JG cells (n=6 primary cultures) significantly increased the medium angiotensin (Ang) II levels from 14±2 to 440±9 pg/ml and suppressed the renin secretion rate (RSR) from 39.6±5.4% to 6.3±1.8% without affecting active renin content (ARC) or total renin content (TRC). In the Aogen-treated cells, the ACEI, delapril hydrochloride (CV3317, 10 μmol/l), significantly decreased the medium Ang II levels to 58±14 pg/ml and increased RSR to 39.8±4.1% without affecting ARC or TRC. The ARB, an active metabolite of candesartan cilexetil (CV11974, 10 μmol/l), however, significantly increased the medium Ang II levels and RSR to 486±15 pg/ml and 40.9±9.8%, respectively, and decreased ARC from 63.2±6.8 to 21.6±3.6 ng of Ang I·h-1. million cells-1 without affecting TRC. The decreases in ARC of the Aogen+CV11974-treated cells (n=6 primary cultures) were inhibited by an Ang II type 2 receptor blocker, PD123319 (10 μmol/l). JG cells (n=6 primary cultures) were also treated with an Ang II type 2 receptor agonist, CGP42212A (0.1 μmol/l). CGP42212A significantly increased RSR from 38.2±1.6% to 49.7±4.7% and decreased ARC from 60.8±3.0 to 25.3±2.8 ng of Ang I·h-1. million cells-1 without affecting TRC. Addition of CV11974 did not alter the RSR, ARC, or TRC of the CGP42212A-treated cells; however, PD123319 abolished the effects of CGP42212A. These results indicate that, distinct from ACEIs, ARBs inhibit prorenin processing of JG cells through Ang II type 2 receptors. Long-term treatment with an ARB may decrease PRA in part by diminishing the storage of active renin in JG cells.

Original languageEnglish
Pages (from-to)915-921
Number of pages7
JournalHypertension Research
Volume26
Issue number11
DOIs
Publication statusPublished - 2003 Nov

Keywords

  • Angiotensin receptors blockers
  • Angiotensin-converting enzyme inhibitors
  • Angiotensinogen
  • Prorenin
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Ichihara, A., Hayashi, M., Hirota, N., Okada, H., Koura, Y., Tada, Y., Kaneshiro, Y., Tsuganezawa, H., & Saruta, T. (2003). Angiotensin II type 2 receptor inhibits prorenin processing in juxtaglomerular cells. Hypertension Research, 26(11), 915-921. https://doi.org/10.1291/hypres.26.915