Published Online
on November 24, 2003

A more recent version of this article appeared on December 16, 2003

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Submitted on February 24, 2003
Revised on August 4, 2003
Accepted on August 12, 2003

Ouabain- and Marinobufagenin-Induced Proliferation of Human Umbilical Vein Smooth Muscle Cells and a Rat Vascular Smooth Muscle Cell Line, A7r5

Joel Abramowitz PhD, Cuiping Dai , Karen K. Hirschi PhD, Renata I. Dmitrieva PhD, Peter A. Doris PhD, Lijun Liu PhD, and Julius C. Allen PhD^*

From the Departments of Medicine, Section of Cardiovascular Sciences (J.A., J.C.A.), Molecular and Cellular Biology (J.A., C.D., K.K.H.), Pediatrics (C.D., K.K.H.), and Molecular Physiology and Biophysics (J.C.A.) and the DeBakey Heart Center (J.C.A.), Baylor College of Medicine, and the Institute of Molecular Medicine, University of Texas (R.I.D., P.A.D.), Houston, Tex; and the Department of Pharmacology, Medical College of Ohio, Toledo (L.L.). Dr Abramowitz is now at the Division of Intramural Research, National Institutes of Environmental Health Sciences, Research Triangle Park, NC.

^* To whom correspondence should be addressed. E-mail: juliusa{at}bcm.tmc.edu.

Background--We studied the growth-promoting effects of 2 sodium pump-selective cardiotonic steroids, ouabain and marinobufagenin, on cultured cells from vascular smooth muscle (VSMCs) from human umbilical vein and a rat VSMC line, A7r5.

Methods and Results--Both ouabain and marinobufagenin activated proliferation of these cells in a concentration-dependent manner, reflecting the cardiotonic steroid sensitivity of the specific ₁ subunit contained within each cell source. The observed effective concentration ranges of both compounds was below that necessary to induce cytoplasmic ion alterations by sodium pump inhibition.

Conclusions--These data indicate that the ouabain-activated proliferative effect previously observed in canine VSMCs occurs in other VSMC sources. This growth effect seems to be initiated by drug interaction with the sodium pump, reflected by the affinity of the steroid for the pump, and is independent of altered transmembrane ionic gradients.

Key words: cells • drugs • muscle, smooth • vasculature

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