Sesamin induces nitric oxide and decreases endothelin-1 production in HUVECs: possible implications for its antihypertensive effect.
OBJECTIVE
Sesamin has been proved to be antihypertensive. Nitric oxide (NO) is the most important vascular relaxing factor that is regulated in endothelium. Endothelin-1 (ET-1) is characterized as a potent vasoconstrictor and is also regulated in endothelium. Alterations in the endothelial production of NO and ET-1 are known to correlate with hypertension. This study investigated the effect of sesamin on NO and ET-1 in the human umbilical vein endothelial cells (HUVECs).


METHODS
The concentrations of NO and ET-1 in the medium of HUVECs treated by sesamin were measured. The mRNA and protein expressions of nitric oxide synthase (NOS), endothelin converting enzyme-1 (ECE-1), and endothelin-1 (ET-1) were also investigated. Other than the mRNA and protein expression, NOS activity and cyclic GMP (cGMP) were detected.


METHODS
The NO concentration was detected by colorimetric assay. The cGMP and ET-1 were analyzed by EIA. The eNOS, ECE-1, and ET-1 mRNA expressions were assayed by Northern blot. The eNOS and ECE-1 protein expressions were analyzed by Western blot. The NOS activity was assayed by detecting the level of [H]-1-citrullin transformed from [H]-1-arginine.


RESULTS
Sesamin not only increased the NO concentration in the medium of HUVECs in a dose-dependent manner after 24 h, but also induced eNOS mRNA and protein expressions. NOS activity in the HUVECs was also induced by sesamin. The content of cGMP was induced by sesamin through NO signaling. On the other hand, the ET-1 concentration in the medium of HUVECs treated by sesamin was suppressed in a dose-dependent manner after 24 h. The ECE-1 protein and mRNA expressions were also inhibited by sesamin. However, the mRNA expression of prepro ET-1 was not influenced by sesamin.


CONCLUSIONS
From the above results, it is suggested that sesamin may improve hypertension by its ability to induce NO and inhibit ET-1 production from endothelial cells. The increase of NO by sesamin is through the induction of eNOS gene expression. The decrease of ET-1 by sesamin is through the inhibition of ECE gene expression, but is not through the inhibition of prepro ET-1 gene expression.
Lee
Chun-Chung
CC
Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Chen
Pey-Rong
PR
Lin
Shankung
S
Tsai
Shiow-Chwen
SC
Wang
Bao-Wei
BW
Chen
Wei-Wen
WW
Tsai
Chingmin E
CE
Shyu
Kou-Gi
KG
D000959:Antihypertensive Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000235:genetics; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D006152:Cyclic GMP / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D019332:Endothelin-1 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D000072396:Endothelin-Converting Enzymes; D004790:Enzyme Induction; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008666:Metalloendopeptidases; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000959:Antihypertensive Agents; D003470:Culture Media; D004149:Dioxoles; D019332:Endothelin-1; D017705:Lignans; D012333:RNA, Messenger; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes; D006152:Cyclic GMP; C054125:sesamin