Effect of Calcium Channel Blockers on Endothelin-1 Production by HDL in Cultured Human Proximal Tubular Cells.
- Author:
Seon Ho AHN
;
Ju Hung SONG
- Publication Type:Original Article
- Keywords:
High density lipoprotein;
Endothelin-1;
Proximal tubular cell;
Calcium channel blockers
- MeSH:
Calcium Channel Blockers*;
Calcium Channels*;
Calcium*;
Cell Count;
Diltiazem;
Endothelin-1*;
Ethanol;
Humans*;
Lipoproteins;
Nifedipine;
Protein Kinase C;
Radioimmunoassay;
Type C Phospholipases;
Verapamil
- From:Korean Journal of Nephrology
1998;17(5):673-678
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Human high density lipoprotein (HDL) is known to stimulate endothelin-1 (ET-1) production through the phospholipase C (PLC)/Ca2+/ protein kinase C (PKC) pathway. Calcium channel blockers may be involved in the decrease of HDL- induced ET-1 production. This study was designed to evaluate whether HDL-induced ET-1 production was affected by Ca2+ channel blockers in cultured human proximal tubular cells (PTC). METHODS: The human PTC were obtained from human nephrectomized tissues, and cultured in six different media, which were bovine serum free (SF) DMEM/F12 medium alone, and five other SF DMEM/F12 media with 200 microgram/ml of HDL, with 200 microgram/ml of HDL and each 10 micrometer of diltiazem, nifedipine, and verapamil solved in 100% ethanol 0.1 volume%, and with 200 microgram/ml of HDL and 0.1 volume% of 100% ethanol as a control. After 24 hours of exposure, ET-1 in the supernatant was measured by radioimmunoassay, and ET-1 level in each well were marked as pg ET-1/mg cell protein/ 24 hr in consideration of cell count. RESULTS: In SF medium, ET-1 production was 1.803+/-0.295pg/mg cell protein/24 hr. In SF medium with 200 microgram/ml of HDL, ET-1 production significantly increased from 1.803+/-0.295 to 10.860+/-0.476 pg/mg cell protein/24 hr (P<0.05). In SF medium with 200 microgram/ml of HDL and 100% ethanol 0.1 volume%, ET-1 production significantly decreased from 10.860+/-0.476 to 6.700+/-1.273pg/mg cell protein/ 24 hr (P<0.05). In SF media with 200 microgram/ml of HDL and each 10 micrometer of diltiazem, nifedipine, and verapamil solved in 100% ethanol 0.1 volume%, ET- 1 production was decreased from 6.700+/-1.273 to 4.043+/-1.550 by diltiazem (P<0.05), to 3.260+/-0.752pg/ mg cell protein/24 hr by verapamil (P<0.05), and to 4.414+/-1.567pg/mg cell protein/24 hr by nifedipine (P=0.067). CONCLUSION: These results suggest that the HDL- induced ET-1 production in cultured human PTC was significantly decreased by diltiazem and verapamil, and it seemed to be decreased by nifedipine.
