[Inhibition of signal transduction pathways of endothelin-1-induced proliferation of vascular smooth muscle cells by nitric oxide].
The signal transduction pathways of the inhibitory effect of nitric oxide (NO) on endothelin (ET)-induced proliferation of vascular smooth muscle cells (VSMCs) were studied. 3H-thymidine (TdR) incorporation, mitogen-activated protein kinase (MAPK) activity and protein kinase C (PKC) activity of cultured VSMCs of rabbits thoracic aorta were measured in the presence of either NO precursor L-arginine (L-Arg) or NO donor 3-morpholino sydnonimine-hydrochloride (SIN-1), or ET-1 alone or with L-Arg or SIN-1. The results show: (1) ET-1 (10(-8) mol/L) significantly increased VSMCs 3H-TdR incorporation (5 times, P < 0.01), MAPK activity (4 times, P < 0.01) and PKC activity (3 times, P < 0.01), as compared with control. L-Arg or SIN-1 alone was without effect on 3H-TdR incorporation, MAPK activity and PKC activity. (2) When ET-1 and L-Arg (2, 5, 10 mmol/L) were simultaneously administered, 3H-TdR incorporation and activity of both MAPK and PKC were all significantly decreased in comparison with the ET group. (3) When ET-1 + SIN-1 (5, 10, 50 mumol/L), the effects coincide with those of the ET-1 + L-Arg groups. These findings indicate that NO inhibition of the signal transduction pathways of the ET-1-induced proliferation of VSMCs may be mediated by the inhibition of ET-1-induced activation of both PKC and MAPK.
Zheng
H Z
HZ
Department of Physiology, Guangdong Medical College, Zhanjiang 524023.
An
G S
GS
Nie
S H
SH
Tang
C S
CS
Liu
N K
NK
Wang
S H
SH
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001120:Arginine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*
D019332:Endothelin-1; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases