Pressure and Angiotensin II Synergistically Induce Aortic Fibronectin Expression in Organ Culture Model of Rabbit Aorta: Evidence for a Pressure-Induced Tissue Renin-Angiotensin System

• Published in: Circulation research Vol. 79; no. 1; pp. 70 - 78
• Main Authors: Bardy, Nathalie, Merval, Regine, Benessiano, Joelle, Samuel, Jane-Lyse, Tedgui, Alain
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.07.1996; Lippincott
• Subjects: Angiotensin II - pharmacology; Animals; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; Arterial hypertension. Arterial hypotension; Arteries - cytology; Arteries - drug effects; Arteries - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Experimental diseases; Fibronectins - genetics; Fibronectins - metabolism; Fluorescent Antibody Technique; In Situ Hybridization; Male; Medical sciences; Organ Culture Techniques; Pressure; Rabbits; Radioimmunoassay; Renin-Angiotensin System - physiology; RNA, Messenger - metabolism; Hypertension; Animal model; Rabbit; Cardiovascular disease; Lagomorpha; Gene expression; In vitro; Fibronectin; Renin angiotensin system; Vertebrata; Mammalia; Aorta; Extracellular matrix; Blood pressure; Hemodynamics; Angiotensin II; Vascular wall
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.79.1.70

Aortic fibronectin (FN) expression is augmented in hypertension. Increasing evidence suggests that both angiotensin II (Ang II) and mechanical factors may induce vascular remodeling in response to hypertension. We have previously shown that, in vitro, increased transmural pressure enhances FN expression in rabbit aortic media. To investigate the existence of a link between the effects of pressure and Ang II and to explore the mechanisms underlying such a relationship, we quantified the effect of Ang II and Ang II inhibitors on the pressure-dependent FN expression in a 3-day organ culture model of rabbit aorta using immunolabeling analysis and detected FN mRNAs by in situ hybridization. A dose-dependent effect of Ang II on FN expression was observed at both 80 and 150 mm Hg but not at 0 mm Hg (relaxed vessels). One micro mol/L Ang II increased the media cross-sectional surface, showing FN expression from 7.9 plus minus 0.7% (n equals 9) to 18.9 plus minus 1.1% (n equals 4) at 80 mm Hg (P less than .01) and from 17.4 plus minus 1.8% (n equals 9) to 56.6% plus minus 3.6 (n equals 4) at 150 mm Hg (P less than .001). In situ hybridization revealed that Ang II and pressure upregulated FN mRNA expression. Losartan, an AT1 antagonist, not only blocked the Ang II effect but also inhibited the transmural pressure effect. Angiotensin-converting enzyme inhibition abolished the pressure-dependent FN expression and significantly diminished the effect of pressure in the presence of Ang II. The effect of renin-angiotensin system inhibitors was specific for FN, since neither bFGF nor laminin expression was affected by these agents. Taken together, the results demonstrate that (1) the effect of transmural pressure is mediated by the stimulation of a local renin-angiotensin system, resulting in a net Ang II production in the culture medium, (2) transmural pressure and Ang II act synergistically to enhance vascular FN expression, (3) AT1 receptors mediate both the effects of pressure and of exogenous Ang II, and (4) the effect of Ang II on FN expression is regulated at a pretranslational level.(Circ Res. 1996;79:70-78.)