Myogenic tone attenuates pressure-induced gene expression in isolated small arteries

Abstract

This study was designed to determine whether pressure-induced expression of early response genes in the arterial wall is dependent on an increase in cell stretch or an increase in wall stress. Mesenteric arteries (245 to 385 microm in diameter) were isolated from Wistar rats and subjected to static pressures of either 90 mm Hg (control), 140 mm Hg, or 165 mm Hg for a period of 3 hours. Arteries developed a range of myogenic tone such that wall stresses in the 140 and 165 mm Hg arteries (1.60 to 4.44x10(6) dynes/cm2) were equivalent in some cases to those of controls (1.76 to 2.63x10(6) dynes/cm2). Vessels subjected to 140 or 165 mm Hg intraluminal pressure had diameters ranging from 74% to 104% of their relaxed diameter at 90 mm Hg, whereas control vessel diameters ranged from 88% to 100%. At the end of each experiment, vessels were fixed in 10% formalin, embedded in paraffin, and sectioned for in situ hybridization. Wall stress significantly correlated with c-myc mRNA and 18S rRNA expression. Gene expression did not correlate with vessel diameter, expressed as a percentage of the relaxed diameter at 90 mm Hg, ie, cell stretch. The expression of beta-actin mRNA did not differ between vessels and showed no correlation with wall stress, suggesting that the induction of c-myc mRNA and 18S rRNA was part of a specific response. These findings show that in an isolated artery, a pressure stimulus can be perceived as an increase in wall stress, independently of cell stretch. Therefore, wall stress may be the signaling parameter in hypertension where arteries are tonically constricted. The inhibition of gene expression by myogenic constriction may explain why hypertrophy takes place in large arteries during hypertension but not in arterioles where increased tone reduces wall stress.