Down-regulation of endogenous nitric oxide synthase inhibitors on endothelial SK3 expression.
OBJECTIVE
To investigate role of endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) in down-regulation of the expression of endothelial SK3 in atherosclerosis.


METHODS
Apolipoprotein E deficient (apo E(-/-)) mice aged 11 approximately 12 weeks were treated with ADMA (5 mg/kg per day, subcutaneous injection) for 4 weeks. Cultured human umbilical venous endothelial cells (HUVECs) were treated with different concentrations of lysophosphatidylcholine (LPC) or ADMA for 48 h. Plasma levels of ADMA were determined by high performance liquid chromatogram (HPLC); protein and mRNA levels of SK3 in the aortas of mice and cultured cells were detected by immunofluorescence, western blot and RT-PCR, respectively.


RESULTS
Concomitantly with the elevated plasma levels of ADMA, the expressions of both SK3 protein and mRNA in aortas of apo E(-/-) mice were significantly reduced in comparison to those of the wild-type mice. Moreover, 4-week treatment of ADMA made levels of SK3 expression even lower. In cultured HUVECs, either LPC or ADMA notably decreased the expressions of both SK3 protein and mRNA in a concentration dependent manner.


CONCLUSIONS
Endogenous ADMA may be an important factor for down-regulation of the expression of endothelial SK3 in atherosclerotic animals.
Zhou
Zhi
Z
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Jiang
De-Jian
DJ
Jia
Su-Jie
SJ
Xiao
Hong-Bo
HB
Xiao
Bo
B
Li
Yuan-Jian
YJ
D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D050197:Atherosclerosis / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology
D001057:Apolipoproteins E; C406328:KCNN3 protein, human; C496900:Kcnn3 protein, mouse; D051640:Small-Conductance Calcium-Activated Potassium Channels; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase