Mechanisms of Oroxylin A-induced Relaxation of Porcine Cerebral Arteries
| Autor: | PO-YI TSAI, 蔡伯宜 |
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| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 Oroxylin A (Oro-A), a flavonoid isolated from Scutellariae baicalensis, is beneficial in ameliorating cardiovascular dysfunctions. Its role in regulating cerebral arterial tone and blood flow, however, remains unclear. This study was designed to assess possible effects of Oro-A on cerebral vascular smooth muscle tone regulation. Results from in vitro tissue bath studies indicated that Oro-A (100 nM – 30 μM) in a concentration-dependent manner relaxed U46619 (a thromboxane A2 receptor agonist, 0.2 μM)-precontracted porcine basilar arterial rings. The vasorelaxation was not affected by denudation of the endothelium (EC). Nor was it affected by SQ22536 (an adenylate cyclase inhibitor, 200 μM) or H89 (an inhibitor for protein kinase A, 10 μM). The Oro-A-induced relaxation of U46619-precontracted arteries, however, was blocked by ODQ (a soluble guanylate cyclase inhibitor, 3-10 μM), tetraethylammonium (TEA, 1 and 10 mM), PNU-37883 and glipizide (3-10 μM and 30 μM, respectively; ATP-sensitive K-channel blockers), and iberiotoxin and charybodotoxin (100 nM; Ca2+-activated K+ channel blockers). In arteries precontracted by high potassium (60 mM), Oro-A-induced vasorelaxation was drastically decreased. Results from two-electrode voltage clamp studies indicated that Oro-A did not affect voltage-activated BKca currents. Furthermore, in the absence of active muscle tone, constriction of the EC-denuded basilar arteries induced by phorbol 12,13-dibutyrate (an activator of PKC, 70 nM) was blocked by Oro-A in a concentration-dependent manner. These results suggest that Oro-A induces EC-independent K-channel-mediated dilation of the basilar arteries. The vasorelaxation, however, is not due to direct opening of the BKca-channels but is indirectly mediated by mechanisms involving activation of the soluble guanylate cyclase, and inhibition of PKC in the smooth muscle cells. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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