Pressor and renal hemodynamic effects of the novel angiotensin A peptide are angiotensin II type 1A receptor dependent

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...

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Vydané v:Hypertension (Dallas, Tex. 1979) Ročník 57; číslo 5; s. 956
Hlavní autori: Yang, Rui, Smolders, Ilse, Vanderheyden, Patrick, Demaegdt, Heidi, Van Eeckhaut, Ann, Vauquelin, Georges, Lukaszuk, Aneta, Tourwé, Dirk, Chai, Siew Yeen, Albiston, Anthony L, Nahmias, Clara, Walther, Thomas, Dupont, Alain G
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.05.2011
Predmet:
Angiotensin II Type 1 Receptor Blockers - pharmacology
Angiotensins - metabolism
Angiotensins - pharmacology
Animals
Benzimidazoles - pharmacology
Blood Pressure - drug effects
Blood Pressure - physiology
Dose-Response Relationship, Drug
Hypertension - metabolism
Kidney - drug effects
Kidney - metabolism
Male
Mice
Mice, Knockout
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Receptor, Angiotensin, Type 1 - genetics
Receptor, Angiotensin, Type 1 - metabolism
Renal Circulation - drug effects
Renal Circulation - physiology
Statistics, Nonparametric
Tetrazoles - pharmacology
Vasoconstriction - drug effects
Vasoconstriction - physiology
ISSN:1524-4563, 1524-4563
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1524-4563
1524-4563
DOI:10.1161/HYPERTENSIONAHA.110.161836