Effects of blockade of AT1 and AT2 receptors in brain on the central angiotensin II pressor response in conscious spontaneously hypertensive rats

G. M. Toney, J. P. Porter

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Intracerebroventricular (i.c.v.) administration of angiotensin II (ANG II) increases vascular resistance and arterial pressure by increasing the activity in the sympathetic nervous system (SNS-component) and secretion of vasopressin (VP-component). This study examined the role of AT1 and AT2 receptors in brain in mediating the exaggerated central cardiovascular effects of ANG II in conscious, adult (10 weeks) spontaneously hypertensive rats (SHR). Mean arterial pressure, heart rate and renal blood flow responses to intraventricular injection of ANG II (100 ng in 5 μl) were determined 10 min after intraventricular administration of the AT1 receptor antagonist losartan alone (1.0, 2.5, 5.0, 10.0 μg), the AT2 receptor ligand PD 123319 alone (3.5 x [10-6, 10-4, 10-2, 10°] μg), or both ligands in combination. In control rats, intraventricular administration of losartan prevented the pressor and renal vascular resistance responses to intraventricular injection of ANG II, in a dose-dependent manner (P <0.05), while intraventricular injection of PD 123319 was ineffective. Likewise, when the SNS- and VP-components were studied individually by preventing the VP-component with a VI receptor antagonist (i.v.) or the SNS-component with chlorisondamine (i.v.), losartan (i.c.v.) prevented both components, while PD 123319 (i.c.v.) was without affect. In addition, doses of losartan, combined with 3.5 μg PD 123319, were no more effective in preventing the pressor or renal vascular resistance responses than losartan, administered alone, suggesting that the VP- and SNS-components of the pressor response to ANG II (i.c.v.) are mediated primarily by AT1 receptors in brain in conscious spontaneously hypertensive rats. In contrast activation of AT2 receptors did not appear to be involved in either pressor component.

Original languageEnglish (US)
Pages (from-to)581-589
Number of pages9
JournalNeuropharmacology
Volume32
Issue number6
DOIs
StatePublished - Jun 1993

Keywords

  • AT1
  • AT2
  • PD 123319
  • angiotensin II
  • arterial pressure
  • brain
  • intracerebroventricular
  • losartan
  • spontaneously hypertensive rat

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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