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(Hypertension. 2000;35:1160.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Activation of MAPKs in Proximal Tubule Cells From Spontaneously Hypertensive and Control Wistar-Kyoto Rats

Astrid Parenti; Xiao-Lan Cui; Ulrich Hopfer; Marina Ziche; Janice G. Douglas

From the Division of Hypertension (A.P., X.-L.C., J.G.D.), Department of Medicine, and the Department of Physiology and Biophysics (U.H.), School of Medicine, Case Western Reserve University and University Hospitals, Cleveland, Ohio; and the Department of Pharmacology (A.P.) and CIMMBA (M.Z.), University of Florence, Florence, Italy.

Correspondence to Dr Janice G. Douglas, Division of Hypertension, Department of Medicine W165, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4982. E-mail jgd3{at}po.cwru.edu

Abstract—The aim of this study was to test the hypothesis that differences exist in the activity and/or expression of mitogen-activated protein kinases (MAPKs) between spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) and that these differences may account for the enhanced activity of the Na⁺/H⁺ exchanger (NHE) previously observed in the renal proximal tubule of SHR. Therefore, the activities of c-jun N-terminal kinase₁ (JNK₁), extracellular signal-regulated kinase_1/2 (ERK_1/2), and p38 were investigated. A reduced amount of ERK₁ and JNK₁ protein was found in renal cortex specimens of SHR as compared with WKY; however, their activities were the same. To study the cellular basis of this difference, immortalized proximal tubule cell lines were grown on Millicell-CM filter inserts where the cell lines organize as polarized monolayers with separate access to apical and basolateral compartments. Although basal JNK₁ and ERK_1/2 activities were not significantly different between WKY and SHR cells, anisomycin stimulated JNK₁ activity in WKY cells more than in SHR cells (eg, at 15 minutes 300% versus 30%, respectively). Similarly, angiotensin II increased JNK₁ and ERK_1/2 activity in a time- and concentration-dependent manner in WKY cells but not in SHR cells. Western blot analyses showed a deficit in JNK₁ and ERK₁ protein in SHR (0.25 and 0.5, respectively, of the levels in WKY cells), although ERK₂ and p38 protein levels were the same. These observations suggest that, although angiotensin II activates MAPKs and MAPKs have been shown to regulate NHE, this regulatory pathway is unlikely to account for the increased activity of NHE in the proximal tubular epithelium of SHR.

Key Words: epithelial cells • protein kinases • hypertension, essential • angiotensin II

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