Role of AT1 receptors and autonomic nervous system in mediating acute pressor responses to ANG II in anesthetized mice

Trinity J. Bivalacqua, Ajay Dalal, Hunter C. Champion, Philip J. Kadowitz

Research output: Contribution to journalArticlepeer-review

Abstract

Hemodynamic responses to angiotensin II and the role of AT1 and AT2 receptors and the autonomic nervous system in mediating acute responses to angiotensin II were investigated in anesthetized CD1 mice. Injections of angiotensin II caused dose-related increases in systemic arterial pressure that were antagonized by candesartan. Pressor responses to angiotensin II were not altered by PD-123,319 in doses up to 25 mg/kg iv. At the lowest dose studied (20 μg/kg iv), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 pg/kg iv) the dose-response curve for angiotensin II was shifted to the right in a nonparallel manner with inhibitory effects that could not be surmounted. The inhibitory effects of candesartan were selective and were similar in animals pretreated with enalaprilat (1 mg/kg iv) to reduce endogenous angiotensin II production. Acute pressor responses to angiotensin II were not altered by propranolol (200 μg/kg iv), phentolamine (200 μg/kg iv), or atropine (1 mg/kg iv) but were enhanced by hexamethonium (5 mg/kg iv). Increases in total peripheral resistance induced by angiotensin II were inhibited by the AT1-receptor antagonist but were not altered by AT2-, α-, or β-receptor antagonists. These results suggest that acute pressor responses to angiotensin II are mediated by AT1 receptors, are buffered by the baroreceptors, and are not modulated by effects on AT2 receptors and that activation of the sympathetic nervous system plays little if any role in mediating rapid hemodynamic responses to the peptide in anesthetized CD1 mice.

Original languageEnglish (US)
Pages (from-to)E838-E847
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume277
Issue number5 40-5
DOIs
StatePublished - Nov 1999
Externally publishedYes

Keywords

  • AT receptors
  • Angiotensin II
  • Cardiac output
  • Heart rate
  • Mouse
  • Systemic arterial pressure

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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