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(Hypertension. 2001;37:955.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Src Tyrosine Kinases and Extracellular Signal–Regulated Kinase 1/2 Mitogen-Activated Protein Kinases Mediate Pressure-Induced C-Fos Expression in Cannulated Rat Mesenteric Small Arteries

Jos P. M. Wesselman; Anca D. Dobrian; Suzanne D. Schriver; Russell L. Prewitt

From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk.

Correspondence to J.P.M. Wesselman, PhD, Department of Pharmacology and Toxicology, University Maastricht, PO Box 616, 6200 MD Maastricht, Netherlands. E-mail j.wesselman{at}farmaco.unimaas.nl

Chronic hypertension is associated with remodeling of small arteries. There is evidence that the high pressure itself may cause these structural changes, but the responsible mechanisms are not clearly defined. Previously we showed that pressure-induced c-fos expression in intact cannulated rat mesenteric small arteries was inhibited by genistein, a general tyrosine kinase inhibitor. The purpose of this study was to further unravel the underlying signal transduction mechanisms, and we particularly tested the involvement of src tyrosine kinases and extracellular signal–regulated kinase (ERK). Rat mesenteric small arteries were cannulated in a dual-vessel chamber. After a 60-minute equilibration period, the pressure in 1 artery was increased to 140 mm Hg, while the other artery remained at 90 mm Hg. Semiquantitative reverse transcriptase–polymerase chain reaction was used to determine c-fos expression, and Western blotting was used to examine levels of ERK phosphorylation. The involvement of src and ERK was tested with the inhibitors herbimycin A (1 µmol/L), PP1 (10 µmol/L), PP2 (10 µmol/L), and PD98059 (30 µmol/L). One-hour exposure to 140 mm Hg increased the c-fos/cyclophilin ratio 3.6-fold, from 0.29±0.07 to 1.06±0.25. All the tested inhibitors suppressed the pressure-induced increase of c-fos expression. A 5-minute exposure period to 140 mm Hg increased ERK phosphorylation, and this was abolished in the presence of PP1. The results suggest that pressure-induced c-fos expression in intact cannulated rat mesenteric small arteries may be mediated, at least in part, by src tyrosine kinases and ERK.

Key Words: arteries • remodeling • pressure • signal transduction • proto-oncogene proteins c-fos • src-family kinases • protein kinases

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