Functional role of brain AT1 and AT2 receptors in the central angiotensin II pressor response

Glenn M. Toney, James P. Porter

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Intracerebroventricular (i.c.v.) angiotensin II (ANG II) increase vascular resistance and elicits a pressor response characterized by sympathetic nervous system activation (SNS component) and increased vasopressin (VP) secretion (VP component). This study examines the role of brain AT1 and AT2 ANG II receptors in mediating the pressor and renal hemodynamic effects of i.c.v. ANG II in conscious Sprague-Dawley rats. Mean arterial pressure, heart rate and renal vascular resistance responses to i.c.v. ANG II (100 ng in 5 μl) were determined 10 min after i.c.v. injection of either the AT1 receptor antagonist, DuP 753 (1.0, 2.5, 5.0, 10.0 μg), the AT2 receptor ligand, PD 123319 (3.5 × [10-6, 10-4, 10-2, 100 μg), or both. In control rats, i.c.v. DuP 753 prevented the pressor response and the increase in renal vascular resistance that occurred following i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 was without affect. When the VP- and SNS components were studied individually, by preventing the SNS component with intravenous (i.v.) chlorisondamine or the VP component with a V1 receptor antagonist (i.v.) similar results were obtained; DuP 753 prevented the SNS component and significantly reduced the VP component. These results indicate that both central ANG II pressor components are mediated primarily by brain AT1 receptors. However, doses of DuP 753 were more effective when combined with 3.5 μg of PD 123319 than when given alone (P < 0.05), suggesting that the pressor effects of i.c.v. ANG II may involve activation of multiple ANG II receptor subtypes.

Original languageEnglish (US)
Pages (from-to)57-63
Number of pages7
JournalBrain Research
Volume603
Issue number1
DOIs
StatePublished - Feb 12 1993

Keywords

  • AT1
  • AT2
  • Angiotensin receptor subtype
  • Blood pressure
  • Intracerebroventricular

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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