The neurogenic origin of hypertension in SHR may be mediated by angiotensin II through a receptor different from AT1 and AT2

M. C. Paré, S. Maltais, E. Escher

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

In spontaneously hypertensive rats (SHR) 15-18 weeks old, the intracerebroventricular (icv) administration of peptide angiotensin II (Ang) antagonists results in a short (30-60 min) decrease (15-25 mmHg) of blood pressure (BP). Both EXP-3174, a known metabolite of Losartan and AT1 selective, and PD-123177, a receptor AT2 specific compound, do not affect SHR BP following icv administration. The recoptor AT1 selective non-peptide Ang antagonists, Losartan and L-158809, induce long-lived (days) significant BP reductions (≤ 40 mmHg) in SHR, but only 18 h after icv injection. The slow development of BP reduction and its persistence might be due to the formation of an active metabolite, different from EXP-3174, a Losartan metabolite. In older SHR (25-28 weeks), the hypotensive effect of Losartan and L-158809 is not significant. These results suggest that in the CNS of the young SHR, an active Renin-Ang-System is implicated in the establishment of the hypertensive state, and that the receptor for this function is different from AT1 and AT2, since it has a selectivity profile different from AT1 and AT2 receptor types.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalRegulatory Peptides
Volume47
Issue number1
DOIs
StatePublished - Aug 13 1993

Keywords

  • Angiotensin antagonist
  • Blood pressure regulation
  • Intracerebroventricular
  • Losartan

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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