ELEVATED PRESSURE STIMULATES PROTOONCOGENE EXPRESSION IN ISOLATED MESENTERIC-ARTERIES

The aim of this study was to determine whether an increase in pressure alone is a sufficient stimulus in isolated small arteries to induce t he immediate early genes that are associated with vascular wall growth . Mesenteric arteries (303-506 mu m diam) were isolated from Wistar ra ts and subjected to static pressure of 90 mmHg (control) or 140 mmHg ( hypertensive). The arteries possessed little active tone or myogenic r esponse to pressure elevation; therefore, both sets of vessels were st retched by similar amounts, but wall stress in the hypertensive vessel s was 60-80% above that of controls. After 30, 60, 180, and 360 min, t he arteries were fixed in Formalin, embedded in paraffin, and sectione d for in situ hybridization. The levels of mRNA for c-fos increased in the hypertensive arteries 2.33-fold at 30 min and 6.64-fold at 60 min . mRNA for c-myc increased 5.13-fold at 60 min and 5.25-fold at 180 mi n. After this early response gene induction, 18S rRNA increased in hyp ertensive vessels: 3.35-fold at 180 min and 4.2-fold at 360 min. These changes were not the result of a nonspecific activation of total gene expression in hypertensive vessels, inasmuch as levels of mRNA for p- actin did not differ from controls; however, hypertensive and control vessels showed increases at 60 min. These results indicate that increa sed pressure is a sufficient stimulus for protooncogene induction and rRNA production in vascular smooth muscle cells in the arterial wall a nd suggest that the mechanical signal is wall stress. Therefore, this model represents a unique tool to complement cultured cells for the st udy of the signaling pathways in the mechanotransduction of a pressure stimulus.