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Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension
Mayo Medical School, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Medical Scientist Training Program, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Department of Laboratory Medicine & Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Division of Nephrology & Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
* Author to whom correspondence should be addressed.
Received: 12 August 2013; in revised form: 30 August 2013 / Accepted: 2 September 2013 / Published: 10 September 2013
Abstract: Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.
Keywords: renovascular hypertension; renin-angiotensin-aldosterone system; oxidative stress; inflammation
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Hartono, S.P.; Knudsen, B.E.; Zubair, A.S.; Nath, K.A.; Textor, S.J.; Lerman, L.O.; Grande, J.P. Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension. Int. J. Mol. Sci. 2013, 14, 18640-18656.
Hartono SP, Knudsen BE, Zubair AS, Nath KA, Textor SJ, Lerman LO, Grande JP. Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension. International Journal of Molecular Sciences. 2013; 14(9):18640-18656.
Hartono, Stella P.; Knudsen, Bruce E.; Zubair, Adeel S.; Nath, Karl A.; Textor, Stephen J.; Lerman, Lilach O.; Grande, Joseph P. 2013. "Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension." Int. J. Mol. Sci. 14, no. 9: 18640-18656.