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Importance of Intracellular Angiotensin II in Vascular Smooth Muscle Cell Apoptosis: Inhibition by the Angiotensin AT1 Receptor Antagonist Irbesartan

Importance of Intracellular Angiotensin II in Vascular Smooth Muscle Cell Apoptosis: Inhibition by the Angiotensin AT1 Receptor Antagonist Irbesartan

Emilio Ruiz, Santiago Redondo, Eugenia Padilla, Antonio Gordillo-Moscoso, Mercedes Salaices, Gloria Balfagón, Teresa Tejerina

Eur J Pharmacol. 2007 Jul 19;567(3):231-9.

PMID: 17509562

Abstract:

The intracellular uptake of Angiotensin II has been described, although its physiological role is not yet understood. We aimed to study the role of Angiotensin II internalization in Angiotensin II-induced apoptosis. Vascular smooth muscle cells were cultured from male Wistar-Kyoto rats and treated with Angiotensin II (1 microM, 48 h). Apoptosis was assessed by DNA fragmentation, cell cytometry and caspase-3 activity. The Angiotensin AT(1) receptor antagonist irbesartan (0.1-10 microM) and the inhibitors of Angiotensin II internalization phenylarsine oxide (PAO, 20 microM), but not the AT(2) receptor antagonist PD123319 (S-(+)-1-[(4-(Dimethylamino)-3-methylphenyl)methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid di(trifluoroacetate) salt), decreased Angiotensin II-mediated apoptosis. Pre-treatment with irbesartan, but not with PD123319, blocked Angiotensin II internalization. We found a strong correlation between intracellular Angiotensin II staining and Angiotensin II-induced apoptosis for all compared groups. We therefore conclude that internalization of Angiotensin II is involved in apoptosis of vascular smooth muscle cells induced by this peptide.

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Catalog Number	Product Name	Structure	CAS Number	Price
ALP1270083243	Spadin trifluoroacetate salt		1270083-24-3 (free base)	Price
ALP51833762	Angiotensin A trifluoroacetate salt		51833-76-2 (free base)	Price

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