Ethanol abrogates angiotensin II-stimulated vascular smooth muscle cell growth.
BACKGROUND
Aberrant vascular smooth muscle cell (VSMC) proliferation is one of the etiological factors for hypertension and stroke. Angiotensin II (Ang II) and ethanol (EtOH) have been shown to modulate the proliferation of vascular smooth muscle cells (VSMCs) individually, but the combined effects of Ang II and EtOH on VSMC proliferative activities are unknown. The objective of this study was to determine the effects of EtOH, Ang II, and the combination of Ang II and EtOH on DNA synthesis, cell number, cyclic AMP (cAMP) production, and Mitogen-Activated Protein Kinase (MAPK) or (p44/42) activities in murine primary VSMCs.


METHODS
Cell growth was determined by [3H] thymidine incorporation and confirmed by cell counts using a hemacytometer. Cyclic AMP assays were carried out using commercially available kits. MAPK activity was determined by immunoprecipitation studies using an ELK-1 fusion protein as a substrate.


RESULTS
Ang II (10 microM) stimulated DNA synthesis by four-fold (P < 0.05), cAMP production by 50% (P < 0.05), and MAPK (p44/42) activities by more than seven-fold (P < 0.01). In contrast, EtOH (100 mM) had no significant effects on DNA synthesis, cell number, and cAMP production. Ethanol exacerbated cAMP production by several fold but inhibited MAPK activity and subsequent cell growth induced by Ang II.


CONCLUSIONS
These results suggest that EtOH elicits a regulatory effect on the Ang II signaling pathway.
Cain
Monique L
ML
Molecular Genetics and Molecular and Cellular Signaling Laboratory, Department of Biology, and National Institutes of Health Center for Environmental Health, Jackson State University, Jackson, MS 39217, USA.
Hester
Robert L
RL
Izevbigie
Ernest B
EB
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D000804:Angiotensin II; D000431:Ethanol; D004247:DNA; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3