Contrasting effects of intervention with ETa and ETb receptor antagonists in hypertension induced by angiotensin II and high-salt diet

Erika I. Boesen, Jennifer S. Pollock, David M. Pollock

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Endothelin (ET) receptor antagonists are antihypertensive and renoprotective in angiotensin II (AngII)-induced hypertension if administered when AngII infusion commences, but their effects on established hypertension are poorly understood. We therefore tested the effects of intervening with an ETA (ABT-627) or ETB (A-192621) receptor antagonist after establishing hypertension with AngII (65 ng/min s.c.) plus 8% NaCl diet (AngII-HS) in rats. Prior to administration of ABT-627, AngII-HS and AngII-HS plus ABT-627 groups displayed robust hypertension (mean arterial pressure (MAP), 170 ± 5 and 165 ± 5 mm Hg versus 110 ± 3 mm Hg in normal salt control rats at day 7, P < 0.05). Administering ABT-627 from day 8 of AngII-HS treatment prevented further rises in MAP (168 ± 5 and 191 ± 3 mm Hg at day 13 in AngII-HS plus ABT-627 and AngII-HS, P < 0.001), without blunting the significant increases in urinary protein (19-fold), albumin (25-fold), or MCP-1 excretion (6-to 8-fold) or the reduction in creatinine clearance. Administering A-192621 from day 8 mildly exacerbated AngII-HS induced hypertension (P < 0.05 for AngII-HS versus AngII-HS plus A-192621 on days 11 and 12 only) and reduced plasma nitrite/nitrate concentration (P < 0.05), without affecting proteinuria, albuminuria, or creatinine clearance. These results confirm the importance of ETA receptor signaling in maintaining AngII-HS hypertension and suggest that including ETB receptor blockade in therapeutic approaches to treating hypertension would be ineffective or even counterproductive.

Original languageEnglish (US)
Pages (from-to)802-807
Number of pages6
JournalCanadian journal of physiology and pharmacology
Volume88
Issue number8
DOIs
StatePublished - Aug 1 2010

    Fingerprint

Keywords

  • A-192621
  • ABT-627
  • Angiotensin II
  • Endothelin
  • Hypertension
  • Kidney

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this