| Autor: |
van Esch, Joep H. M., Schuijt, Martin P., Sayed, Jilani, Choudhry, Yawar, Walther, Thomas, Jan Danser, A. H. |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Jun2006, Vol. 148 Issue 4, p452-458, 7p, 16 Graphs |
| Abstrakt: |
Angiotensin (Ang) II type 2 (AT2) receptors are believed to counteract Ang II type 1 (AT1) receptor-mediated effects. Here, we investigated AT2 receptor-mediated effects on coronary and cardiac contractility in C57BL/6 mice.Hearts were perfused according to Langendorff. Baseline coronary flow (CF) and left ventricular systolic pressure (LVSP) were 2.7±0.1 ml min−1 and 111±3 mmHg (n=50), respectively.Ang II (n=14) concentration dependently decreased CF and LVSP, by maximally 41±4 and 25±3%, respectively (pEC50s 7.41±0.12 and 7.65±0.12). The AT1 receptor antagonist irbesartan (n=4) abolished all Ang II-induced changes, whereas the AT2 receptor antagonist PD123319 (n=6) enhanced (P<0.05) the effect of Ang II on CF (to 59±1%) and LVSP (to 44±2%), without altering its potency. A similar enhancement was observed in the presence of nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester HCl (L-NAME; n=4). On top of L-NAME, PD123319 no longer affected the response to Ang II (n=4).The AT2 receptor agonist CGP42112A (n=4) did not affect CF or LVSP, nor did CGP42112A (n=4) alter the constrictor response to the α1-adrenoceptor agonist phenylephrine. Furthermore, Ang II exerted no effects in hearts of AT1A−/− mice (n=5), whereas its effects in hearts of AT1A+/+ wild-type control mice (n=7) were indistinguishable from those in hearts of C57BL/6 mice.In conclusion, Ang II exerts opposite effects on coronary and cardiac contractility in the mouse heart via activation of AT1A and AT2 receptors. AT2 receptor-mediated effects depend on NO and occur only in conjunction with AT1A receptor activation.British Journal of Pharmacology (2006) 148, 452–458. doi:10.1038/sj.bjp.0706762; published online 8 May 2006 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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