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Carvedilol inhibits vascular smooth muscle cell proliferation
C P Sung1, A J Arleth, E H Ohlstein
1Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
Journal of Cardiovascular Pharmacology
|February 1, 1993
Summary
Carvedilol significantly inhibits vascular smooth muscle cell proliferation, acting as an antimitogenic agent. This effect was concentration-dependent and reversible, distinguishing it from other beta-blockers.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Cell Biology
Background:
- Vascular smooth muscle cell (VSMC) proliferation contributes to cardiovascular diseases.
- Antihypertensive agents are being investigated for broader cellular effects.
Purpose of the Study:
- To evaluate the antiproliferative effects of carvedilol on rat aortic VSMCs.
- To compare carvedilol's effects with other beta-adrenoceptor antagonists and a calcium channel blocker.
Main Methods:
- Cultured rat aortic VSMCs were treated with carvedilol at various concentrations.
- Mitogenesis was assessed by [3H]thymidine incorporation.
- Responses to growth factors (endothelin-1, thrombin, EGF, PDGF, angiotensin II) were measured.
Main Results:
- Carvedilol demonstrated concentration-dependent inhibition of basal and stimulated VSMC mitogenesis.
- The IC50 for carvedilol's inhibitory effect was approximately 1 microM.
- Carvedilol's antimitogenic effect was reversible and not shared by labetalol, celiprolol, or sotalol, but was seen with propranolol.
Conclusions:
- Carvedilol possesses significant antiproliferative properties on VSMCs.
- Its mechanism differs from non-selective beta-blockers and calcium channel blockers.
- Carvedilol's antimitogenic action may contribute to its therapeutic benefits in hypertension.