High glucose enhances mitogenic response to endothelin-1 in rabbit vascular smooth muscle cells.
OBJECTIVE
To examine the effects of high glucose on the mitogenic response of rabbit aortic vascular smooth muscle cells (VSMC) to endothelin-1 (ET-1).


METHODS
VSMC were cultured in normal glucose (5.5 mmol.L-1), high glucose (25 mmol.L-1) or high osmolality (glucose 5.5 mmol.L-1, plus mannitol 19.5 mmol.L-1). DNA synthesis was measured by [3H]thymidine incorporation. The expression of phospho-p44/42 MAPK was determined by Western blot.


RESULTS
At a concentration range from 10(-12) to 10(-8) mol.L-1, ET-1 stimulated [3H]thymidine incorporation and phospho-p44/42 MAPK expression in VSMC in a concentration-dependent manner. From 10(-11) to 10(-8) mol.L-1, the mitogenic effect of ET-1 was higher in VSMC cultured in high glucose at equivalent concentration than cells cultured in normal glucose or high osmolality (P < 0.05 or P < 0.01), but no marked difference was observed in the growth response between cells cultured under the latter two conditions. Similarly, ET-1 increased expression of phospho-p44/42 MAPK by 60%-65% in VSMC cultured in high glucose, compared with cells in normal glucose or high osmolality.


CONCLUSIONS
VSMC cultured in high glucose exhibited increased mitogenic response to ET-1, which seemed to be related to the enhanced expression of phospho-p44/42 MAPK.
Guo
X
X
Laboratory of Molecular Pharmacology, Hu-nan Medical University, Changsha, China.
Liu
W L
WL
Yi
F X
FX
Guo
Z G
ZG
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D011817:Rabbits
D019332:Endothelin-1; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D005947:Glucose