Elevated pressure stimulates proto-oncogene expression in isolated mesenteric arteries. Allen, Steven P., Hong Mei Liang, Michael A. Hill, and Russell L. Prewitt. Department of Physiology, Eastern Virginia Medical School, Norfolk, VA 23501
APStracts 3:0157H, 1996.
The aim of this study was to determine whether an increase in pressure alone is a sufficient stimulus in isolated small arteries to induce the immediate-early genes which are associated with vascular wall growth. Mesenteric arteries (303-506 [mu]m diameter) were isolated from Wistar rats and subjected to static pressures of either 90 mm Hg (control) or 140 mmHg (hypertensive). The arteries possessed little active tone or myogenic response to pressure elevation, therefore, both sets of vessels were stretched similar amounts but wall stress in the hypertensive vessels was 60-80% above that of controls. Following 30, 60, 180, and 360 minutes the arteries were fixed in formalin, embedded in paraffin and sectioned for in situ hybridization. The levels of mRNA for c-fos increased in the hypertensive arteries 2.33-fold at 30 minutes and 6.64-fold at 60 minutes. mRNA for c-myc increased 5.13-fold at 60 minutes and 5.25 -fold at 180 minutes. Following this early-response-gene induction, 18S rRNA increased in hypertensive vessels, 3.35-fold at 180 minutes and 4.2-fold at 360 minutes. These changes were not the result of a non-specific activation of total gene expression in hypertensive vessels as levels of mRNA for [beta]-actin did not differ from controls, however both hypertensive and control vessels showed increases at 60 minutes. These results indicate that increased pressure is a sufficient stimulus for proto-oncogene induction and rRNA production in vascular smooth muscle cells in the arterial wall and suggest that the mechanical signal is wall stress. Therefore this model represents a unique tool to complement cultured cells for the study of the signaling pathways in the mechanotransduction of a pressure stimulus. 

Received 25 September 1995; accepted in final form 8 April 1996.
APS Manuscript Number H902-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 23 April 96