Importance of intracellular angiotensin II in vascular smooth muscle cell apoptosis: inhibition by the angiotensin AT1 receptor antagonist irbesartan |
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Authors: | Ruiz Emilio Redondo Santiago Padilla Eugenia Gordillo-Moscoso Antonio Salaices Mercedes Balfagón Gloria Tejerina Teresa |
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Affiliation: | Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Av. Complutense, s/n. 28040 Madrid, Spain. |
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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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Keywords: | Vascular smooth muscle cell Angiotensin Apoptosis Internalization Cell trafficking |
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