(Hypertension. 1999;34:132-137.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Genistein Inhibits Pressure-Induced Expression of c-fos in Isolated Mesenteric Arteries
From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Va.
Correspondence to Russell L. Prewitt, PhD, Department of Physiological Sciences, Eastern Virginia Medical School, PO Box 1980, Norfolk, VA 23501. E-mail rlp{at}borg.evms.edu
Abstract—We have previously demonstrated that elevating intraluminal pressure from 90 to 140 mm Hg in isolated mesenteric arteries increases the expression of proto-oncogenes. These proto-oncogenes encode nuclear transcription factors that regulate the expression of target genes during various stages of the cell cycle. Thus, pressure-induced proto-oncogene expression may represent a mechanism by which pressure can induce growth and/or proliferation of vascular smooth muscle. The purpose of this study was to determine the intracellular signals that contribute to the pressure-induced increase in c-fos expression. Small mesenteric arteries were isolated from male Wistar rats and transferred to a dual-vessel chamber. The arteries were cannulated and slowly equilibrated to initial conditions (90 mm Hg, 37°C) while being continuously superfused with a HEPES-bicarbonate–buffered Krebs' solution. After the equilibration period, the intraluminal pressure in 1 artery was increased to 140 mm Hg for 1 hour. In experiments designed to determine the intracellular signals involved in the pressure-induced increase in c-fos expression, specific inhibitors were introduced to the superfusate reservoir of both arteries before the pressure increase. The arteries were then fixed in phosphate-buffered formalin and embedded in paraffin blocks. Sections of paraffin-embedded arteries were fixed on slides, and the expression of c-fos was determined by in situ hybridization with the use of 35S-labeled riboprobes. The pressure-induced expression of c-fos was not inhibited by nitrendipine (10 µmol/L), a calcium-free Krebs' solution containing EGTA (1 to 2 mmol/L), calphostin C (0.1 µmol/L), or cytochalasin D (0.4 µmol/L) but was inhibited by genistein (30 µmol/L). The results suggest that activation of a tyrosine kinase is required for pressure-induced c-fos expression, but the signaling pathway does not require extracellular calcium entry, intact actin filaments, or protein kinase C. As we have shown previously, the expression of c-fos correlated with wall stress.
Key Words: arteries • proto-oncogene • muscle, smooth, vascular • stress, wall • blood pressure • rats
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