title: Pressor and renal hemodynamic effects of the novel angiotensin A peptide are angiotensin II type 1A receptor dependent.
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 (AT(1)) or Ang II type 2 (AT(2)) receptors. Intravenous and intrarenal administration of Ang A induced dose-dependent pressor and renal vasoconstrictor responses in normotensive rats, which were blocked by the AT(1) receptor antagonist candesartan but were not altered by the AT(2) receptor ligands PD123319, CGP42112A, or compound 21. Similar responses were observed after intravenous administration in spontaneously hypertensive rats. Deletion of AT(1a) receptors in mice almost completely abolished the pressor and renal vasoconstrictor responses to Ang A, indicating that its effects are mediated via AT(1a) receptors. Ang A was less potent than Ang II in vivo. The in vitro study demonstrated that Ang A is a full agonist for AT(1) receptors, with similar affinity for AT(1) and AT(2) 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.
authors.affiliation: Department of Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Patrick
authors.initials: P
authors.lastname: Vanderheyden
authors.forename: Heidi
authors.initials: H
authors.lastname: Demaegdt
authors.forename: Ann
authors.initials: A
authors.lastname: Van Eeckhaut
authors.forename: Georges
authors.initials: G
authors.lastname: Vauquelin
authors.forename: Aneta
authors.initials: A
authors.lastname: Lukaszuk
authors.forename: Dirk
authors.initials: D
authors.lastname: Tourwé
authors.forename: Siew Yeen
authors.initials: SY
authors.lastname: Chai
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Albiston
authors.forename: Clara
authors.initials: C
authors.lastname: Nahmias
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Alain G
authors.initials: AG
authors.lastname: Dupont
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000809:Angiotensins / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D018709:Statistics, Nonparametric; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000809:Angiotensins; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C516880:angiotensin A; C081643:candesartan