(Hypertension. 2000;36:1053.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Renal Protein Phosphatase 2A Activity and Spontaneous Hypertension in Rats
From the Departments of Pediatrics (P.Y., L.D.A., P.A.J.) and Physiology and Biophysics (P.A.J.), Georgetown University School of Medicine, Washington, DC; the Department of Internal Medicine (G.M.E.), Washington Hospital Center, Washington, DC; the Department of Physiology (U.H.), Case Western Reserve School of Medicine, Cleveland, Ohio; and the Department of Pathology and Medical Automation Research Center (R.A.F.), Charlottesville, Va.
Correspondence to Peiying Yu, MD, Department of Pediatrics, PHC-2, Georgetown University Medical Center, 3800 Reservoir Rd NW, Washington, DC 20007. E-mail yup{at}gunet.georgetown.edu
Abstract—The impaired renal
paracrine function of dopamine in spontaneously hypertensive rats (SHR)
is caused by hyperphosphorylation and desensitization
of the renal D1 dopamine receptor. Protein phosphatase 2A
(PP2A) is critical in the regulation of G-protein–coupled
receptor function. To determine whether PP2A expression and
activity in the kidney are differentially regulated in genetic
hypertension, we examined the effects of a D1-like agonist,
fenoldopam, in renal cortical tubules and immortalized renal proximal
tubule cells from normotensive Wistar-Kyoto rats (WKY) and SHR. In
cortical tubules and immortalized proximal tubule cells,
PP2A expression and activities were greater in cytosol than
in membrane fractions in both WKY and SHR. Although PP2A
expressions were similar in WKY and SHR, basal PP2A
activity was greater in immortalized proximal tubule cells of SHR than
WKY. In immortalized proximal tubule cells of WKY, fenoldopam increased
membrane PP2A activity and expression of the regulatory
subunit PP2A-B56
, effects that were blocked by the
D1-like antagonist SCH23390. Fenoldopam had no
effect on cytosolic PP2A activity but decreased
PP2A-B56 expression. In contrast, in immortalized
proximal tubule cells of SHR, fenoldopam decreased PP2A
activity in both membranes and cytosol but predominantly in the
membrane fraction, without affecting PP2A-B56
expression; this effect was blocked by the D1-like
antagonist SCH23390. We conclude that renal
PP2A activity and expression are differentially regulated
in WKY and SHR by D1-like receptors. A failure of
D1-like agonists to increase PP2A activity in
proximal tubule membranes may be a cause of the increased
phosphorylation of the D1 receptor in
the SHR.
Key Words: hypertension, genetic • receptors, dopamine • dopamine • hypertension, essential • phosphatase
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