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(Hypertension. 1997;30:1613-1620.)
© 1997 American Heart Association, Inc.

Articles

Bosentan Prevents Preglomerular Alterations During Angiotensin II Hypertension

Daniel Casellas; Nathalie Bouriquet; ; Abderraouf Herizi

From the Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France.

Correspondence to Daniel Casellas, PhD, Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, 75 rue de la Cardonille, 34093 Montpellier, Cédex 5, France. E-mail casellas{at}iurc1.iurc.montp.inserm.fr

Abstract The present study was performed to characterize structurofunctional alterations of preglomerular vessels during chronic angiotensin II (Ang II)–induced hypertension (Ang II group: 400 ng · kg^-1 · min^-1, 10 days) and to assess the role of endothelin-1 in rats receiving Ang II and the mixed receptor antagonist bosentan (Ang II+B group: 30 mg · kg^-1 · d^-1, 10 days). Systolic blood pressure rose by 56±3 and 54±6 mm Hg in Ang II and Ang II+B rats, respectively. Albuminuria increased similarly in both Ang II–treated groups, reflecting glomerular barrier dysfunction. Preglomerular vessels were isolated after HCl maceration and comprised arcuate arteries and their branches, interlobular arteries (ILA), and afferent arterioles (AA). In the Ang II group, focal vascular lesions affected 36±6%, 20±5%, and 4±1% of arcuate arterial branches, ILA, and AA, respectively. They were characterized by 74% increased media thickness and accumulation of Sudan black–positive (SB⁺) lipid droplets, and media cell proliferation was documented through immunohistochemistry. The occurrence of SB⁺ lesions was strikingly reduced with bosentan. Autoregulatory responses (AR) were assessed along ILA and AA with the use of blood-perfused juxtamedullary nephron preparations. AR were elicited by raising blood perfusion pressure from 60 to 160 mm Hg and quantified through videomicroscopy as pressure-induced constrictions. AR were inhibited in Ang II–treated rats along ILA and AA; Ang II–induced AR changes were prevented by bosentan. Maximal relaxation induced by Mn²⁺ revealed equal basal tone in Ang II–treated, Ang II+B–treated, and control vessels. Chronic Ang II–induced hypertension is therefore associated with the development of SB⁺ lesions and selective impairment of AR in juxtamedullary nephrons. Endothelin-1 likely mediates the structurofunctional alterations of preglomerular vasculature during Ang II hypertension.

Key Words: nephrons • autoregulation • basal tone • glomerulopathy • endothelin

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