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(Hypertension. 1996;27:897-905.)
© 1996 American Heart Association, Inc.

Articles

Angiotensin II Is Mitogenic for Cultured Rat Glomerular Endothelial Cells

Gunter Wolf; Fuad N. Ziyadeh; Gunther Zahner; Rolf A.K. Stahl

From the Department of Medicine, Division of Nephrology and Osteology, University of Hamburg (Germany), and the Renal-Electrolyte and Hypertension Division and the Penn Center for Molecular Studies of Kidney Diseases, University of Pennsylvania School of Medicine, Philadelphia, Pa (F.N.Z.).

Correspondence to Gunter Wolf, MD, University of Hamburg, University Hospital Eppendorf, Department of Medicine, Division of Nephrology and Osteology, Pavilion 61, Martinistraße 52, D-20246 Hamburg, FRG.

Abstract Angiotensin II (Ang II) has growth-stimulatory properties on different renal cell types. However, possible growth effects of this vasoactive peptide on endothelial cells isolated from the glomerular microvasculature have not formally been investigated. Therefore, we isolated and characterized primary cultures of rat glomerular endothelial cells. We used a simple technique in which collagenase-treated glomeruli were sparsely plated in several 96-well culture plates and microscopically screened for cobblestone-like outgrowth. After two limiting dilutions, homogeneous cultures were obtained. Cells were characterized by positive staining for the endothelial markers factor VIII, CD 31, endothelial leukocyte adhesion molecule-1, and the lectin Bandeiraea simplificifolia. Ang II stimulated the synthesis and release of endothelin-1 in culture supernatants. Moreover, in contrast to syngeneic mesangial cells, glomerular endothelial cells expressed angiotensin-converting enzyme. Ang II stimulated a mild but significant proliferation of quiescent cells, as measured by [³H]thymidine incorporation and direct cell counting. This mitogenesis was transduced by losartan-blockable angiotensin type 1 receptors. Moreover, Ang II mediated phosphorylation of mitogen-activated protein kinase 2 and induction of transcripts for the immediate early gene Egr-1. Our results indicate that Ang II is a moderate mitogen for primary cultures of rat glomerular endothelial cells and activation of these metabolically active cells may play a role in the pathophysiology of several types of glomerulonephritis. Moreover, remodeling of glomerular endothelial cells by Ang II may be important in the progression of structural renal damage during the course of hypertensive injury.

Key Words: angiotensin II • hyperplasia • glomerular endothelial cells • proto-oncogenes • protein kinases

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