Functional roles of brain AT1 and AT2 receptors in the central angiotensin II pressor response in conscious young spontaneously hypertensive rats

Glenn M. Toney, James P. Porter

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Areas of adult rat brain that mediate the cardiovascular effects of central angiotensin II (ANG II) predominately express AT1 ANG II receptors. In contrast, AT2 receptor expression in young rats is transiently increased, reaching a maximum during the first few weeks of life. This study was designed to determine the roles of brain AT1 and AT2 receptors in mediating the central pressor effects of ANG II in young (4-week-old) conscious spontaneously hypertensive rats (SHR). Mean arterial pressure responses to intracerebroventricular (i.c.v.) ANG II (100 ng in 5 μl) were determined 10 minutes after i.c.v. injection of either the AT1 receptor antagonist Losartan (1.0, 2.5, 5.0, and 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. Losartan prevented the pressor response to i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 alone was without effect. In other animals, pressor responses caused by i.c.v. ANG II-induced vasopressin secretion (VP-component) and sympathetic nervous system activation (SNS-component) were studied individually, with similar result; Losartan prevented the SNS-component, but reduced the VP-component by only 45%, indicating that both pressor components involve AT1 receptor activation. However, doses of Losartan were more effective when combined with 3.5 μg of PD 123319 than when given alone (P < 0.05); nearly eliminating the VP-component. These results suggest that i.c.v. ANG II-induced pressor effects may involve activation of multiple receptor subtypes.

Original languageEnglish (US)
Pages (from-to)193-199
Number of pages7
JournalDevelopmental Brain Research
Volume71
Issue number2
DOIs
StatePublished - Feb 19 1993

Keywords

  • Angiotensin II
  • Blood pressure
  • Intracerebroventricular
  • Losartan
  • PD 123319
  • Spontaneously hypertensive rat

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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