Inhibition of human vascular smooth muscle cell proliferation by the novel multiple-action antihypertensive agent carvedilol.
We examined the antiproliferative effect of the novel multiple-action antihypertensive agent carvedilol on human vascular smooth muscle cells (VSMC). Carvedilol inhibited the increase in cell number induced by foetal calf serum (FCS) in 86% (18 of 21) of human VSMC grown both from saphenous vein (17.6 +/- 3.5% inhibition, mean +/- SEM, n = 15) and restenotic lesions (31.4 +/- 5.5% inhibition, mean +/- SEM, n = 5). Carvedilol had a greater antiproliferative effect than other beta-adrenoceptor antagonists. In comparison with calcium channel blockers, carvedilol (10 microM) elicited a degree of growth inhibition similar to that of verapamil, but was less effective than the dihydropyridine amlodipine at equimolar concentrations. Although carvedilol had a greater antiproliferative effect on cells derived from restenotic lesions cells than on control saphenous vein cells, the difference was not statistically significant. In the present study, the antiproliferative effect of carvedilol on human VSMC in vitro occurred at concentrations higher than those in plasma. Although this may represent a limitation to the clinical efficacy of carvedilol against proliferation of VSMC associated with hypertension and atherosclerosis, the apparent relative selectivity of carvedilol for restenosis-derived cells is a promising line of investigation.
Patel
M K
MK
Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science Technology & Medicine, London, England.
Chan
P
P
Betteridge
L J
LJ
Schachter
M
M
Sever
P S
PS
D000959:Antihypertensive Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D012501:Saphenous Vein / Q000166:cytology / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D014652:Vascular Diseases / Q000473:pathology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D007770:L-Lactate Dehydrogenase; D013936:Thymidine