Effects of the angiotensin II type-1 receptor antagonist ZD7155 on angiotensin II-mediated regulation of renin secretion and renal renin gene expression, renal vasoconstriction, and blood pressure in rats

Kraemer, Bernhard K. and Ritthaler, Theresia and Schweda, Frank and Ittner, Karl Peter and Scholz, Holger and Riegger, Guenter A. J. and Kurtz, Armin (1998) Effects of the angiotensin II type-1 receptor antagonist ZD7155 on angiotensin II-mediated regulation of renin secretion and renal renin gene expression, renal vasoconstriction, and blood pressure in rats. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 31 (5). pp. 700-705. ISSN 0160-2446, 1533-4023

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Abstract

Angiotensin Ui receptors have recently been subclassified as type-1 or type-2 receptors. The in vitro and in vivo effects of blocking the angiotensin TI type-1 receptor with ZD7155, an angiotensin II type-1 selective receptor antagonist, have been studied in angiotensin Ii-mediated increases in cytosolic calcium in rat mesangial cells, in angiotensin II-induced renal and systemic vasoconstriction, and in angiotensin II-mediated regulation of renin secretion and renal renin gene expression. ZD7155 completely blocked the ability of angiotensin II to elicit an increase in free intracellular calcium concentrations in rat mesangial cells. In isolated perfused rat kidneys, ZD7155 completely abolished the angiotensin II-induced vasoconstriction and increased renin secretion to 700% of baseline levels. Furthermore. ZD7155 decreased systolic blood pressure by 16 mm Hg, increased plasma renin activity 3.7-fold, and stimulated renal renin gene expression 4.2-fold in Sprague-Dawley rats in vivo. Our results suggest that ZD7155 is a potent antagonist of the angiotensin II type-1 receptor, which mediates angiotensin II-induced increases of free intracellular calcium concentrations in (e.g., renal mesangial cells), constriction of the renal and systemic vasculature, and inhibition of renin secretion and synthesis.

Item Type: Article
Uncontrolled Keywords: SIGNAL-TRANSDUCTION; CELLS; KIDNEY; SR-47436; SUBTYPES; LOSARTAN; angiotensin II; renin secretion; angiotensin II type-1 receptor antagonist; ZD7155; blood pressure; renal vasoconstriction
Subjects: 500 Science > 570 Life sciences
600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Anästhesiologie
Medicine > Lehrstuhl für Innere Medizin II
Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz
Depositing User: Dr. Gernot Deinzer
Date Deposited: 23 May 2023 13:11
Last Modified: 23 May 2023 13:11
URI: https://pred.uni-regensburg.de/id/eprint/49846

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