Resistance to mineralocorticoids in the wistar-furth rat.
Ullian, Michael E., Muhammad M. Islam, Christopher J. Robinson, Wayne
R. Fitzgibbon, Eric T. Tobin, Richard V. Paul.
Ralph H. Johnson Veterans Administration Medical Center and Medical
University of South Carolina, Charleston, South Carolina
APStracts 3:0523H, 1996.
Wistar-Furth rats (WF) do not develop hypertension when treated with
salt and mineralocorticoids and, therefore, may be useful for
investigating the mechanisms of mineralocorticoid action and
hypertension. In the present studies, we determined vascular and
renal responses of WF to mineralocorticoids. Control Wistar rats (W)
developed DOCA-NaCl and dexamethasone hyper tension, whereas WF rats
developed dexamethasone hypertension only. Aldosterone treatment of
vascular smooth muscle cells cultured from WF resulted in 82% less
upregulation of angiotensin II radioligand binding, 50% less
induction of angiotensin II AT1a receptor mRNA, and 76% less po
tentiation of angiotensin II-stimulated inositol phosphates than did
aldosterone treatment of cells from W. Similarly, DOCA-NaCl
potentiated angiotensin II- and phenylephrine-stimulated contractions
in aortic rings from W but not from WF. Although DOCA-NaCl treatment
effected hypokalemia to an equal degree in WF and W, increases in
renal citrate synthase activity (a specific renal mineralocor ticoid
response) were greater in W compared to WF. WF manifest a partial
defect in mineralocorticoid responsiveness in vascular smooth muscle
and, possibly, in the kidney.
Received 1 May 1996; accepted in final form 30 September 1996.
APS Manuscript Number H389-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996