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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Patcharin
P
Tep-areenan
Phongphat
P
Wetchasit
Pattara
P
Sawasdee
D000818:Animals; D029061:Annonaceae / Q000737:chemistry*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D010936:Plant Extracts; D006710:Homocysteine; C007957:homocysteine thiolactone