Extracted Anaxagorea luzonensis A. Gray Restored Impairment of Endothelium-Dependent Vasorelaxation Induced by Homocysteine Thiolactone in Rat Aortic Rings

Tep-areenan, P.; Wetchasit, P.; Sawasdee, P.

Journal of the Medical Association of Thailand 98 Suppl. 10: S31-S37

2015


ISSN/ISBN: 0125-2208
PMID: 27276830
Document Number: 16522
To investigate the beneficial effects of Anaxagorea luzonensis (AL) extract on homocysteine thiolactone (HTL)-induced impairment of endothelium-dependent relaxation in rat aortic rings. The mechanisms involved in the effects of AL on endothelial dysfunctions by HTL are also examined. Aortic rings from male Wistar rats were co-incubated for 90 minutes with L-arginine (3 mM), a precursor of nitric oxide (NO); superoxide dismutase (SOD, 200 U/mL), a scavenger of superoxide anion; indomethacin (10 µM), a cyclooxygenase (COX) inhibitor; SC560 (10 µM), a COX-1 inhibitor; NS398 (10 µM), a COX-2 inhibitor; or SQ29548 (1 µM), a thromboxane A₂ receptor antagonist in the presence of HTL (1 mM). After 90 minutes of incubation period, the rings were pre-contracted with methoxamine, and then carbachol was cumulatively added to the bath. AL (1 and 3 µg/mL) was co-incubated with 1 mM HTL in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME, 300 µM), a NO synthase inhibitor and p-hydroxymercurybenzoate (PHMB, 10 µM), a sulfhydryl group blocking agent. Changes in tension were measured using an isometric force transducer and recorded on the PowerLab. Endothelium-dependent vasorelaxation to carbachol was impaired after exposure of aortic rings to HTL (0.3 and 1 mM). The inhibitory effects of HTL (1 mM) on relaxant responses to carbachol were restored by L-arginine, SOD, indomethacin, SC560 and SQ29548, but not NS398. Interestingly, AL reduced impairment of vasorelaxation induced by HTL (1 mM). However, L-NAME and PHMB largely inhibited the protective effects of AL. These results suggest that HTL-induced impairment of endothelium-dependent vasorelaxation may occur via decreased NO release, and generation of oxygen free radical. This study first shows that enhancement of TxA₂ production via COX-1 pathway is involved in HTL-induced endothelial dysfunctions. The protective effects of AL on impairment of relaxation by HTL may be related to increasing NO production and sulfhydryl-dependent.

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