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 the immediate early genes that are associated with vascular wall growth. Mesenteric arteries (303-506 microm diam) were isolated from Wistar rats and subjected to static pressure of 90 mmHg (control) or 140 mmHg (hypertensive). The arteries possessed little active tone or myogenic response to pressure elevation; therefore, both sets of vessels were stretched by similar amounts, but wall stress in the hypertensive vessels was 60-80% above that of controls. After 30, 60, 180, and 360 min, 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 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 min. After this early response gene induction, 18S rRNA increased in hypertensive 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 beta-actin did not differ from controls; however, hypertensive and control vessels showed increases at 60 min. These results indicate that increased pressure is a sufficient stimulus for protooncogene 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.
Department of Physiology, Eastern Virginia Medical School, Norfolk 23501, USA.
S P
SP
Allen
H M
HM
Liang
M A
MA
Hill
R L
RL
Prewitt
D000199:Actins / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D015870:Gene Expression; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
D000199:Actins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S