Effect of SR 33805 on arterial smooth muscle cell proliferation and neointima formation following vascular injury.

Abstract

The possible activity of SR 33805 ([[N-[dimethoxy-3,4-phenethyl]-N- methylamino-propoxyl]-4-benzenesulfonyl]-2-isopropyl-3-methyl-1-in dole), a novel Ca2+ channel blocker, in early atherogenesis was investigated. In vitro, SR 33805 strongly inhibited fetal calf serum-induced proliferation of cultured human aortic smooth muscle cells with an IC50 value of 0.3 +/- 0.1 microM (n = 3). In this respect, SR 33805 was several fold more active than the reference compounds: diltiazem, verapamil, nifedipine and fantofarone. SR 33805 was also a potent inhibitor of platelet-derived growth factor- or basic fibroblast growth factor-induced proliferation of human smooth muscle cells. SR 33805 inhibited serum-stimulated 45Ca2+ uptake in these cells, with an IC50 value of 47 +/- 18 nM. The effect of SR 33805 on intimal smooth muscle hyperplasia in rabbit carotid arteries subjected to air-drying endothelial injury was then investigated. After a 16-day treatment, SR 33805 (6.0 mg/kg/day p.o.) inhibited the development of intimal thickening. Under the same experimental conditions, nifedipine, verapamil, diltiazem (2 x 6 mg/kg/day p.o.--16 days) and fantofarone (12 mg/kg/day p.o.--16 days) were inactive. These results show that SR 33805, a novel and potent Ca2+ channel blocker, can reduce myointimal thickening following endothelial injury.

• Authors: F Dol, P Schaeffer, I Lamarche, A M Mares, P Chatelain, J M Herbert
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 280 Issue 2 Pg. 135-42 (Jul 04 1995) ISSN: 0014-2999 [Print] Netherlands
• PMID: 7589177 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Calcium Radioisotopes
• Indoles
• Sulfones
• Fibroblast Growth Factor 2
• SR 33805
• Epidermal Growth Factor
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Radioisotopes
• Carotid Arteries (pathology)
• Carotid Artery Injuries
• Cell Division (drug effects)
• Epidermal Growth Factor (antagonists & inhibitors, pharmacology)
• Fibroblast Growth Factor 2 (antagonists & inhibitors, pharmacology)
• Humans
• In Vitro Techniques
• Indoles (pharmacology)
• Male
• Muscle, Smooth, Vascular (cytology, drug effects, pathology)
• Neovascularization, Pathologic (pathology, prevention & control)
• Rabbits
• Sulfones (pharmacology)