2. Academic Validation
  3. Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus

Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus

  • Hypertension. 2014 Aug;64(2):330-7. doi: 10.1161/HYPERTENSIONAHA.114.03587.
Manuel Gómez-Guzmán 1,  Rosario Jiménez 1,  Miguel Romero 1,  Manuel Sánchez 1,  María José Zarzuelo 1,  Mercedes Gómez-Morales 1,  Francisco O'Valle 1,  Antonio José López-Farré 1,  Francesca Algieri 1,  Julio Gálvez 1,  Francisco Pérez-Vizcaino 1,  José Mario Sabio 1,  Juan Duarte 2
Affiliations

Affiliations

  • 1 From the Department of Pharmacology (M.G.-G., R.J., M.R., M.S., M.J.Z., J.D.), CIBERehd (F.A., J.G.), and Department of Pathology (M.G.-M., F.O.), University of Granada, Granada, Spain; Cardiovascular Research Unit, Hospital Clínico San Carlos (A.J.L.-F.), Department of Pharmacology, School of Medicine, Complutense University of Madrid; Ciber Enfermedades Respiratorias (Ciberes), and Instituto de Investigacion Sanitaria Gregorio Maranon (IISGM), Madrid, Spain (F.P.-V.); Internal Medicine Service, Hospital Universitario Virgen de las Nieves, Granada, Spain (J.M.S.).
  • 2 From the Department of Pharmacology (M.G.-G., R.J., M.R., M.S., M.J.Z., J.D.), CIBERehd (F.A., J.G.), and Department of Pathology (M.G.-M., F.O.), University of Granada, Granada, Spain; Cardiovascular Research Unit, Hospital Clínico San Carlos (A.J.L.-F.), Department of Pharmacology, School of Medicine, Complutense University of Madrid; Ciber Enfermedades Respiratorias (Ciberes), and Instituto de Investigacion Sanitaria Gregorio Maranon (IISGM), Madrid, Spain (F.P.-V.); Internal Medicine Service, Hospital Universitario Virgen de las Nieves, Granada, Spain (J.M.S.). [email protected].
PMID: 24842914 DOI: 10.1161/HYPERTENSIONAHA.114.03587
Abstract

Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of Cardiovascular Disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. Vascular Reactive Oxygen Species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47(phox) were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti-double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications.

Keywords

acute kidney injury; hydroxychloroquine; hypertension; lupus erythematosus, systemic.

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