Antiproliferative effect of L-NAME on rat vascular smooth muscle cells

El Mabrouk, M., Singh, A., Touyz, R.M. and Schiffrin, E.L. (2000) Antiproliferative effect of L-NAME on rat vascular smooth muscle cells. Life Sciences, 67(13), pp. 1613-1623. (doi:10.1016/S0024-3205(00)00744-X)

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Abstract

The nitric oxide synthase (NOS) inhibitor L-NAME may have growth inhibitory effects in vivo. We investigated in vitro the potential growth inhibitory effects of three different NOS inhibitors: L-NAME (1 mM), LNMMA (1 mM) and aminoguanidine (0.5 mM), on fetal bovine serum (FBS) and platelet derived growth factor (PDGF-BB)-stimulated growth in cultured vascular smooth muscle cells (VSMCs). [3H]-thymidine incorporation into rat mesenteric VSMCs was measured as an index of VSMCs proliferation (DNA synthesis) and activation of extracellular signal regulated kinase (ERK1/2), a major signaling event in cell growth, was measured by western blot assay. PDGF-BB (0–5 ng/mL) and FBS (0–5%) increased [3H]-thymidine incorporation in a dose-dependent manner up to 6–10 fold. L-NAME significantly reduced PDGF-BB (5 ng/ml) and FBS (5%) stimulated DNA synthesis by 46% and 38% respectively. The increase of [3H]-thymidine incorporation induced by PDGF-BB and FBS was unaltered by L-NMMA. In contrast, aminoguanidine induced an increase in FBS and PDGF-BB-stimulated [3H]-thymidine incorporation of 64% and 34% respectively above cells not exposed to aminoguanidine. ERK1/2 phosphorylation induced by PDGF-BB and FBS was not affected by pre-treatment with L-NAME or aminoguanidine. In conclusion, NOS inhibitors differentially influence DNA synthesis in VSMCs: L-NAME inhibits FBS and PDGF-BB-stimulated cellular proliferation whereas aminoguanidine accentuates FBS and PDGF-BB-stimulated VSMCs proliferation. These phenomena are independent of the ERK1/2 pathway. The growth inhibitory effects of L-NAME may be related to differences in properties from other NOS inhibitors, and independent of its ability to inhibit NOS.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: El Mabrouk, M., Singh, A., Touyz, R.M., and Schiffrin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Life Sciences
ISSN:0024-3205

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