Predominance of AT1 blockade over mas-mediated angiotensin-(1-7) mechanisms in the regulation of blood pressure and renin-angiotensin system in mRen2.Lewis rats

Jasmina Varagic*, Sarfaraz Ahmad, Jessica L. Voncannon, Norihito Moniwa, K. Bridget Brosnihan, Jan Wysocki, Daniel Batlle, Carlos M. Ferrario

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background We investigated whether the antihypertensive actions of the angiotensin II (Ang II) receptor (AT1-R) blocker, olmesartan medoxomil, may in part be mediated by increased Ang-(1-7) in the absence of significant changes in plasma Ang II. Methods mRen2.Lewis congenic hypertensive rats were administered either a vehicle (n = 14) or olmesartan (0.5mg/kg/day; n = 14) by osmotic minipumps. Two weeks later, rats from both groups were further randomized to receive either the mas receptor antagonist A-779 (0.5mg/kg/day; n = 7 per group) or its vehicle (n = 7 per group) for the next 4 weeks. Blood pressure was monitored by telemetry, and circulating and tissue components of the renin-angiotensin system (RAS) were measured at the completion of the experiments.RESULTSAntihypertensive effects of olmesartan were associated with an increase in plasma renin concentration, plasma Ang I, Ang II, and Ang-(1-7), whereas serum aldosterone levels and kidney Ang II content were reduced. Preserved Ang-(1-7) content in kidneys was associated with increases of ACE2 protein but not activity and no changes on serum and kidney ACE activity. There was no change in cardiac peptide levels after olmesartan treatment. The antihypertensive effects of olmesartan were not altered by concomitant administration of the Ang-(1-7) receptor antagonist except for a mild further increase in plasma renin concentration. Conclusions Our study highlights the independent regulation of RAS among plasma, heart, and kidney tissue in response to AT1-R blockade. Ang-(1-7) through the mas receptor does not mediate long-term effects of olmesartan besides counterbalancing renin release in response to AT1-R blockade.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalAmerican Journal of Hypertension
Volume26
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • AT receptor
  • angiotensin II
  • angiotensin-(1-7)
  • blood pressure
  • heart
  • hypertension
  • kidney
  • mas receptor
  • olmesartan

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Predominance of AT<sub>1</sub> blockade over mas-mediated angiotensin-(1-7) mechanisms in the regulation of blood pressure and renin-angiotensin system in mRen2.Lewis rats'. Together they form a unique fingerprint.

Cite this