Fibronectin Expression and Aortic Wall Elastic Modulus in Spontaneously Hypertensive Rats

From the Institut National de la Santé et de la Recherche Médicale (INSERM) U337 (P.L., Y.B., R.S.C.), Paris; INSERM U441 (J.M.D.L., J.B.), Bordeaux; the Department of Pharmacology, Broussais Hospital (S.L.), Paris; and URA CNRS 879 (P.C.), Saint-Cyr l'Ecole, France.

Correspondence to Patrick Lacolley, MD, PhD, INSERM U337, 12 rue de L'Ecole de Médecine, Paris 75270 Paris Cedex 06, France. E-mail lacolley{at}ccr.jussieu.fr

Abstract—Recent studies have shown that large-artery wall remodeling per se does not reduce distensibility in hypertension, indicating qualitative or quantitative changes in arterial components. The aim of the study was to determine in 1-year-old spontaneously hypertensive rats (SHRs) the changes in the elastic properties of large arteries, as assessed by the incremental elastic modulus (E_inc), and the changes in the extracellular matrix, including fibronectin (FN) and 5ß1-integrin. The relationship between E_inc and circumferential wall stress was calculated from in vivo pulsatile changes in blood pressure and arterial diameter by using a high-resolution echo-tracking system at the site of the abdominal aorta and in vitro medial cross-sectional area. E_inc-stress curves and FN and integrin 5-subunit contents were determined for each animal. Mean stress and E_inc were higher in SHRs than in Wistar rats. However, in a common range of stress, E_inc-stress curves for SHRs were superimposable on those for Wistar rats, indicating that wall materials in both strains have equivalent mechanical behavior. Immunohistochemistry indicated that total FN, EIIIA FN isoform, and 5-integrin increased in the SHRs aortas without changes in elastin and collagen densities. Total FN was also increased in SHRs as determined by Western blot analysis. No differences in FN and 5-subunit mRNAs were detected between SHRs and Wistar rats. These results indicate that the aortic wall material of SHRs and Wistar rats have equivalent mechanical properties, although in SHRs it is subjected to a higher level of stress. By increasing cell-matrix attachment sites, FN may participate in the mechanical adaptation of both cellular and matrix components in SHRs.

Key Words: SHR • elastic modulus • aorta • fibronectin • 5ß1-integrin

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