Effects of arecoline in relaxing human umbilical vessels and inhibiting endothelial cell growth.
This study investigated the effects of arecoline, an active ingredient of the areca nut, on the tone of human umbilical arteries and veins and on the eNOS expression and cell proliferation of human umbilical vein endothelial cells (HUVECs). We found that arecoline relaxes the human umbilical artery and vein rings in a concentration-dependent manner; the higher the concentration of arecoline, the greater the relaxation of the rings. However, the relaxation decreases after the endothelium was removed or pretreated with L-NAME, a nitric oxide synthase inhibitor. Moreover, arecoline increases in a dose-dependent way the cGMP levels of human umbilical arteries and veins. In HUVECs, arecoline also increases the eNOS expression. Therefore, the relaxant effects of arecoline on the umbilical artery and vein rings were endothelium-dependent through the NO-cGMP systems. In addition, arecoline at higher doses (100-1000 microM) inhibits endothelial cell proliferation; the exposure toarecoline (100-1000 microM) for 24 and 48 h induces G2/M cell cycle arrest of HUVECs. Our results indicate that arecoline would decrease vascular tone, in part mediated by NO. Higher doses of arecoline inhibit endothelial cell growth, which suggest that long-term use or high doses of areca nut might induce endothelial dysfunction and associated diseases.
Kuo
Fu-Chen
FC
Department of Gynecology and Obstetrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Wu
Deng-Chyang
DC
Yuan
Shyng-Shiou F
SS
Hsiao
Kwo-Ming
KM
Wang
Yuan-Yung
YY
Yang
Yuan-Chieh
YC
Lo
Yi-Ching
YC
D001114:Areca; D001115:Arecoline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000187:drug effects; D008517:Phytotherapy; D011247:Pregnancy; D014469:Umbilical Arteries / Q000187:drug effects* / Q000378:metabolism; D014471:Umbilical Veins / Q000187:drug effects* / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; D001115:Arecoline; D052250:Nitric Oxide Synthase Type III