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. MATERIAL AND METHOD: 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. CONCLUSION: 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.

Effects of Phikud Navakot extract on vascular reactivity in the isolated rat aorta.

The aim of the present study is to investigate the effect of standardized Phikud Navakot extract (NVKE) on aortic rings from male Sprague Dawley rats. Changes in tension were measured using an isometric force transducer and recorded on the PowerLab recording system. Vasorelaxant effect of NVKE was examined in the presence of indomethacin (10 microM), N(G)-nitro L-arginine methyl ester (L-NAME, 300 microM), methoxamine (0.1-300 microM), carbachol (1 nanoM-30 microM), or sodium nitroprusside (0.1 nanoM-10 microM). The results showed that NVKE (1-300 microg/mL) caused vasorelaxation in a concentration-dependent manner with a pEC50 value of 4.27 +/- 0.24 and R(max) of 67.7 +/- 13.9%. Pretreatment with indomethacin or L-NAME did not affect NVKE-induced vasorelaxation. However, co-incubation of indomethacin and L-NAME significantly reduced (p < 0.05) vasorelaxation to NVKE (100 microg/mL). Pre-treatment with NVKE significantly decreased (p < 0.05) endothelium-dependent relaxations to carbachol (R(max) = 52.90 +/- 14.3%), but not to sodium nitroprusside. Moreover contractions to methoxamine were unaffected after pretreatment with NVKE. The present study suggested that NVKE decreased vasorelaxation to carbachol in the rat aorta, which may exert at least against muscarinic receptors. These findings support the use of Phikud Navakot, a major ingredient of Yahom Navakot, against dizziness and fainting.

Possible mechanisms of vasorelaxation for 5,7-dimethoxyflavone from Kaempferia parviflora in the rat aorta.

The present study investigated the vascular effects of 5,7-dimethoxyflavone (DMF), isolated from the rhizomes of Kaempferia parviflora (KP), on rat isolated aortic rings and its possible mechanisms. DMF (1-100 µM) caused concentration-dependent relaxations in aortic rings precontracted with methoxamine. This effect was significantly reduced by removal of the endothelium, and after pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 300 µM), indomethacin (10 µM) and 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 µM), but not 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536, 100 µM). Relaxant responses to DMF were significantly inhibited by high KCl (60 mM) in both endothelium-intact and -denuded rings. In addition, the relaxations to DMF were significantly reduced by pretreatment with tetraethylammonium (TEA, 5 mM), glibenclamide (10 µM), 4-aminopyridine (1 mM) or barium chloride (10 µM). Preincubation with DMF (10 and 100 µM) for 30 min significantly inhibited the contractile responses to CaCl(2) in a Ca(2+)-free, high K(+) buffer. The present study demonstrated that DMF causes endothelium-dependent relaxation that is partly mediated by NO-cGMP and cyclooxygenase pathways. Interestingly, DMF-induced responses are mainly due to increasing K(+) efflux, and inhibition of Ca(2+) influx from the extracellular space. The vasodilator effects of DMF provide experimental support for the potential use of KP as a medical plant in the treatment of cardiovascular diseases.