Angiotensin II Activates Collagen Type I Gene in the Renal Vasculature of Transgenic Mice During Inhibition of Nitric Oxide Synthesis - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Circulation Year : 1999

Angiotensin II Activates Collagen Type I Gene in the Renal Vasculature of Transgenic Mice During Inhibition of Nitric Oxide Synthesis

Abstract

Background —Hypertension is frequently associated with renal vascular fibrosis. The purpose of this study was to investigate whether angiotensin II (Ang II) is involved in this fibrogenic process. Methods and Results —Experiments were performed on transgenic mice harboring the luciferase gene under the control of the collagen I-α 2 chain promoter [procolα 2 (I)]. Hypertension was induced by chronic inhibition of NO synthesis ( N G -nitro- l -arginine methyl ester, L-NAME). Procolα 2 (I) activity started to increase in the renal vasculature after 4 weeks of L-NAME treatment ( P <0.01) and at 14 weeks reached 3- and 8-fold increases over control in afferent arterioles and glomeruli, respectively ( P <0.001). Losartan, an AT 1 receptor antagonist, given simultaneously with L-NAME prevented the increase of procolα 2 (I) levels and attenuated the development of renal vascular fibrosis without normalizing systolic pressure increase. Because we found previously that endothelin mediated renal vascular fibrosis in the L-NAME model, the interaction between Ang II, endothelin, and procolα 2 (I) was investigated in ex vivo and short-term in vivo experiments. In both conditions, the Ang II–induced activation of procolα 2 (I) in renal cortex was blocked by an endothelin receptor antagonist. Conclusions —During chronic inhibition of NO, the collagen I gene becomes activated, leading to the development of renal vascular fibrosis. Ang II is a major player in this fibrogenic process, and its effect on collagen I gene is independent of systemic hemodynamics and is at least partly mediated by the profibrogenic action of endothelin.
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Dates and versions

inserm-03788594 , version 1 (26-09-2022)

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Jean-Jacques Boffa, Pierre-Louis Tharaux, Sandrine Placier, Raymond Ardaillou, Jean-Claude Dussaule, et al.. Angiotensin II Activates Collagen Type I Gene in the Renal Vasculature of Transgenic Mice During Inhibition of Nitric Oxide Synthesis. Circulation, 1999, 100 (18), pp.1901-1908. ⟨10.1161/01.cir.100.18.1901⟩. ⟨inserm-03788594⟩
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