Blockade of brain "ouabain" prevents sympatho-excitatory
and pressor responses to high sodium in spontaneously hypertensive
rats.
Huang, Bing S., and Frans H. H. Leenen.
Hypertension Unit, Division of Cardiology, University of Ottawa
Heart Institute, Ottawa, Ontario, Canada
APStracts 2:0568H, 1995.
The effects of blockade of brain "ouabain" by central infusion
of antibody Fab fragments, which bind ouabain and brain
"ouabain" with high affinity, on sodium-sensitive
hypertension were studied in spontaneously hypertensive rats (SHR)
from 5 to 9 weeks of age on high or regular sodium diet. The Fab
fragments, or in controls [delta]-globulins were infused
intracerebroventricularly (icv) via osmotic minipump. BP, HR and
renal sympathetic nerve activity (RSNA) and their responses to air
stress and to the [alpha]2-adrenoceptor agonist guanabenz icv were
recorded in conscious rats at 9 weeks. In control SHR but not Wistar
Kyoto rats (WKY), high sodium further increased resting mean arterial
pressure (171+/-3 vs 141+/-4 mmHg in control SHR on regular sodium),
and potentiated excitatory and inhibitory responses of BP, HR and
RSNA to air stress and icv guanabenz, respectively. These effects of
high sodium were all prevented by icv Fab fragments. In SHR on
regular sodium or WKY on either diet, the Fab fragments had no
effects on resting BP or responses to air stress and guanabenz. We
conclude that similar to Dahl salt-sensitive rats, in SHR a sodium
-induced increase in brain "ouabain" is responsible for the
decreased sympatho-inhibition and increased SYMPATHO-excitation and
thus the exacerbation of hypertension. Brain "ouabain"
appears not to be involved in the development of hypertension in SHR
on regular sodium intake.
Received 30 June 1995; accepted in final form 4 December 1995.
APS Manuscript Number H606-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95