• Toxicological Research
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• 제30권3호
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• pp.141-148
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• 2014

Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin ($PGI_2$), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions.

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.209-216
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• 1998

The present study was designed: (1) to determine whether or not hypoxia stimulates the release of endothelium-derived relaxing factors (EDRFs) from endothelial cells, and (2) to examine whether or not the hypoxia-induced EDRFs release is further augmented by previous hypoxia-reoxygenation, using bioassay system. In the bioassay experiment, rabbit aorta with endothelium was used as EDRFs donor vessel and rabbit carotid artery without endothelium as a bioassay test ring. The test ring was contracted by prostaglandin $F_{2{\alpha}}$ $(3{\times}10^{-6}\;M/L)$, which was added to the solution perfusing through the aortic segment. Hypoxia was evoked by switching the solution aerated with 95% $O_2/5%\;CO_2$ mixed gas to one aerated with 95% $N_2/5%\;CO_2$ mixed gas. When the contraction induced by prostaglandin $F_{2{\alpha}}$ reached a steady state, the solution was exchanged for hypoxic one. And then, hypoxia and reoxygenation were interchanged at intervals of 2 minutes (intermittent hypoxia). The endothelial cells were also exposed to single 10-minute hypoxia (continuous hypoxia). When the bioassay ring was superfused with the perfusate through intact aorta, hypoxia relaxed the precontracted bioassay test ring markedly. Whereas, when bioassay ring was superfused with the perfusate through denuded aorta or polyethylene tubing, hypoxia relaxed the precontracted ring slightly. The relaxation was not inhibited by indomethacin but by nitro-L-arginine or methylene blue. The hypoxia-induced relaxation was further augmented by previous hypoxia-reoxygenation and the magnitude of the relaxation by intermittent hypoxia was significantly greater than that of the relaxation by continuous hypoxia. The results suggest that hypoxia stimulates EDNO release from endothelial cells and that the hypoxia-induced EDNO release is further augmented by previous hypoxia-reoxygenation.

• 대한약리학회지
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• 제29권1호
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• pp.65-72
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• 1993

자외선조사는 흰쥐흉부대동맥의 휴지기장력에 거의 영향을 미치지 못했으나, phenylephrine으로 수축된 표본에서는 자외선조사로 내피세포가 존재하면 수축반응을, 내피세포가 제거되면 이완반응이 나타났다. 이 수축반응은 조사시간의 길이($10{\sim}320$초)에 비례하여 증가하였으나 이완반응은 그렇지 못하였다. 내피세포 존재표본에서 자외선의 수축반응은 phenylephrine농도의 증가($10^{-7}{\sim}10^{-5}M$) 그리고 $acetylcholine(10^{-6}M)$, $isoproterenol(10^{-7}M)$ 및 $nitroglycerin(3.5{\times}10^{-8} M)$의 추가투여시 크게 강화되었다. 그러나 $phentolamine(10^{-6}M)$ 또는 $LY83583(10^{-7},10^{-6}M)$의 추가투여시에는 자외선 수축반응이 억제 또는 이완반응으로 역전되었다. 내피세포 제거표본에서의 자외선 이완반응은 phenylephrine농도의 증가 그리고 isoproterenol, nitroglycerine, phentolamine 및 LY83583의 추가투여시 유의하게 감약되었다. 이상의 성적은 흰쥐 적출 흥부대동맥에서 자외선조사는 내피세포 존재유무에 따라 수축과 이완반응이 각각 나타나며, 수축반응은 자외선에 의한 EDRF 유리억제 또는 부분적으로 어떤 EDCF와도 관련이 있음을 시사하고 있다.