Pressor and Renal Hemodynamic Effects of the Novel Angiotensin A Peptide Are Angiotensin II Type 1A Receptor Dependent

Rui Yang, Ilse Julia Smolders, Patrick Vanderheyden, Heidi Demaegdt, Ann Van Eeckhaut, Georges Vauquelin, Aneta Lukaszuk, Dirk Tourwe, Siew Yeen Chai, Anthony Albiston, Clara Nahmias, Thomas Walther, Alain Dupont

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Recently, a new derivative of angiotensin (Ang) II, called "Ang A," has been discovered to be present in plasma of healthy humans and, in increased concentrations, in end-stage renal failure patients. The objectives of the study were to investigate the blood pressure and renal hemodynamic responses to Ang A in normotensive and hypertensive rats and in genetically modified mice and the binding properties of Ang A to Ang II type 1 (AT1) or Ang II type 2 (AT2) receptors. Intravenous and intrarenal administration of Ang A induced dose-dependent pressor and renal vasoconstrictor responses in normotensive rats, which were blocked by the AT1 receptor antagonist candesartan but were not altered by the AT2 receptor ligands PD123319, CGP42112A, or compound 21. Similar responses were observed after intravenous administration in spontaneously hypertensive rats. Deletion of AT1a receptors in mice almost completely abolished the pressor and renal vasoconstrictor responses to Ang A, indicating that its effects are mediated via AT1a receptors. Ang A was less potent than Ang II in vivo. The in vitro study demonstrated that Ang A is a full agonist for AT1 receptors, with similar affinity for AT1 and AT2 receptors as Ang II. Overall, the responses to Ang A and Ang II were similar. Ang A has no physiological role to modulate the pressor and renal hemodynamic effects of Ang II.
Original languageEnglish
Pages (from-to)956-964
Number of pages9
JournalHypertension
Volume57
Issue number5
Publication statusPublished - 2011

Keywords

  • angiotensin A
  • angiotensin II
  • renal blood flow
  • blood pressure
  • AT1 receptors
  • AT2 receptors

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