[Inhibitory effects of D-polymannuronic sulfate on proliferation of rat vascular smooth muscle cells and its related mechanisms of action in vitro].
OBJECTIVE
To investigate the inhibitory effects of D-polymannuronic sulfate (DPS) on the proliferation of rat vascular smooth muscle cells (VSMC) induced by basic fibroblast growth factor (bFGF) or interleukin-1 (IL-1) and its related mechanisms.


METHODS
Rat aortic smooth muscle cells pretreated with DPS in concentrations ranging from 0.001 microgram.mL-1 up to 100 micrograms.mL-1 were incubated at 37 degrees C for 24 h, followed by addition of bFGF (50 ng.mL-1) or IL-1 (50 U.mL-1) for another 24 h. The effects of DPS on the proliferation of VSMC were evaluated by MTT assays. VSMC were pretreated with DPS in concentrations ranging from 0.001 microgram.mL-1 up to 1 microgram.mL-1, followed by addition of L-NAME (0.1 microgram.mL-1) or bFGF (50 ng.mL-1) for 24 h. Supernatant nitric oxide (NO) was determined with NO assay kit, while supernatant angiotensin II (Ang II) and endothelin-1 (ET-1) were measured by radioimmunoassay.


RESULTS
DPS exerted antiproliferative effects at concentrations ranging from 0.01 microgram.mL-1 to 10 micrograms.mL-1, and its maximal effect was observed at the concentration of 1 microgram.mL-1. Also, the suppressing actions of DPS on the proliferation of VSMC were diminished by increasing the concentrations of bFGF or IL-1. Furthermore, DPS increased NO synthesis and decreased Ang II and ET-1 contents released from VSMC in a concentration-dependent manner.


CONCLUSIONS
DPS afforded the antiproliferative effects on bFGF- or IL-1-treated VSMC and its underlying mechanisms were associated with enhancement of NO synthesis and decrement of Ang II and ET-1 production/release in vitro.
Zhu
H B
HB
Department of Marine Pharmacology, Marine Drugs and Food Institute, Ocean University of Qingdao, Qingdao 266003, China.
Geng
M Y
MY
Guan
H S
HS
Zhang
J T
JT
D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D019332:Endothelin-1 / Q000378:metabolism; D006603:Hexuronic Acids / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D000809:Angiotensins; D019332:Endothelin-1; D006603:Hexuronic Acids; C437391:polymannuronic sulfate; D009569:Nitric Oxide