[Effects of angiotensin II receptor blockers, angiotensin converting enzyme inhibitors, 3-hydroxy-3-methyl glutaryl (HMG) CoA reductase inhibitors, amlodipine and epalrestat on cultured basilar artery smooth muscle cell proliferation].

Proliferation of vascular smooth muscle cells (VSMC) stimulated by oxidative stresses and reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. Antiatherosclerotic effects of angiotensin II receptor blockers, angiotensin converting enzyme inhibitors, HMG CoA reductase inhibitors, calcium channel blocker and epalrestat were studied with an in vitro guinea-pig basilar artery smooth muscle cell (GBa-SM3) culture system over 3 days incubated with 0 to 10% of fetal bovine serum. Results demonstrated that simvastatin (0.1 mM), fluvastatin (0.3 mM), amlodipine (0.2 mM) and epalrestat (1 mM) elicited significant (p < 0.05 or 0.01) antiproliferative effects, whereas losartan (1 mM), valsartan (1 mM), enalapril (0.1 mM), captopril (1 mM), trandolapril (0.01 mM), pravastatin (0.7 mM) did not. In conclusion, the present in vitro VSMC culture system may serve as a comprehensive screening method for pleiotropic effects of commonly used therapeutic agents.

[Alterations of antiproliferative effects of serum obtained from patients with acute cerebral infarction treated with a radical scavenger, edaravone, with or without amlodipine using an in vitro cultured basilar artery smooth muscle cells].

The guinea-pig basilar artery smooth muscle cell (GBa-SM3) culture system in the Dulbecco's modified Eagle's medium for 3 days serves as a useful in vitro model for assessing antiproliferative effects of various therapeutic agents on vessels. With use of this system we studied whether human serum obtained from patients with acute cerebral infarction (n = 16) would have a proliferative effect on vessels and whether an administration of a free radical scavenger, edaravone, with or without amlodipine would elicit antiproliferative effects. The control serum was obtained from 3 healthy human subjects. Time courses of the cell growth and survival were measured colorimetrically by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrzolium bromide (MTT) test. The stimulatory effect on the proliferation of GBa-SM3 cells of patients' serum obtained immediately after infarction was significantly (p < 0.05) greater than those obtained from the same patients after the treatment of edaravone for 2 weeks. In addition, the serum obtained from the patients treated by edaravone and amlodipine (n = 7) showed a significantly (p < 0.05) greater antiproliferative effect than that obtained from those treated by edaravone (n = 9). In conclusion, edaravone may have a clinically beneficial antiproliferative effect on vascular smooth muscle cells. Co-administration of amlodipine, possessing an antioxidative calcium channel blocker, with edaravone may be a promising combination to patients with acute cerebral infarction. Further controlled clinical trials with a large number of patients should be warranted.