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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/F1214    most recent 00162.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ideura, H. Articles by Nojima, Y. Search for Related Content PubMed PubMed Citation Articles by Ideura, H. Articles by Nojima, Y.

Angiotensin II provokes podocyte injury in murine model of HIV-associated nephropathy

¹Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan; and ²Kidney Disease Section, Kidney Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Submitted 7 April 2007 ; accepted in final form 17 July 2007

Conditional transgenic mice that express one of the human immunodeficiency virus (HIV)-1 accessory genes, vpr, selectively in podocytes using a podocin promoter and a tetracycline-inducible system develop renal injuries similar to those of patients with HIV-associated nephropathy (HIVAN). We have shown that a heminephrectomy accelerates podocyte injury, which is alleviated by angiotensin II (ANG II) type 1 receptor blocker (ARB). The current study further explores the role of ANG II in the genesis of HIVAN in this murine model. With ANG II infusion, heavy proteinuria was observed at 1 wk after the initiation of doxycycline administration to induce vpr expression in podocytes. Severe morphological and phenotypical changes in the podocytes were observed at 2 wk, together with extensive glomerulosclerosis. Norepinephrine infusion, instead of ANG II, increased the systemic blood pressure to the same level as that achieved using ANG II. However, albuminuria and glomerular injury were modest in norepinephrine-infused mice. Treatment with an ARB, olmesartan, almost completely inhibited glomerular injury. In contrast, lowering the blood pressure with a vasodilator, hydralazine, partially decreased albuminuria but did not produce any histological changes. ANG II infusion alone without doxycycline resulted in a lower level of albuminuria and minimal histological changes. These data demonstrate that excessive ANG II accelerates vpr-induced podocyte injury in a mouse model of HIVAN.

human immunodeficiency virus-associated nephropathy; proteinuria; glomerulosclerosis; angiotensin II type 1 receptor blocker; conditional transgenic mice