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Analysis of responses to angiotensin II in the mouse
Trinity J Bivalacqua
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Hunter C Champion
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Albert L Hyman
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Dennis B McNamara
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Philip J Kadowitz
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA, pkadowi{at}tulane.edu
Responses to angiotensin II (Ang II) were investigated in anaesthetised CD1 mice. Injections of Ang II caused dose-related increases in systemic arterial pressure that were antagonised by candesartan. Responses to Ang II were not altered by PD 123319. At the lowest dose studied (20 µg/kg i.v.), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 µg/kg i.v.), the dose-response curve for Ang II was shifted to the right in a non-parallel manner. The inhibitory effects of candesartan were selective and were similar in animals pretreated with enalaprilat to reduce endogenous Ang II production. Pressor responses to Ang II were not altered by propranolol, phentolamine or atropine, but were enhanced by hexamethonium. Increases in total peripheral resistance were inhibited by the AT1-receptor antagonist (ARB) but were not altered by AT2-receptor, alpha- or beta-receptor antagonists. These results suggest that pressor responses to Ang II are mediated by AT 1-receptors, are buffered by the baroreceptors, are not modulated by effects on AT2receptors, and that activation of the sympathetic nervous system plays little role in mediating rapid haemodynamic responses to the peptide in anaesthetised mice.
Key Words: angiotensin II mouse systemic arterial pressure
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Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl,
S48-S53 (2001)
DOI: 10.1177/14703203010020010801

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