on June 10, 2002
Published online before print June 10, 2002, doi: 10.1161/01.HYP.0000022659.17774.E4
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Submitted on April 10, 2002
From the Hypertension Unit, University of Ottawa Heart
Institute, Ottawa, Ontario,
Canada. * To whom correspondence should be addressed. E-mail: fleenen{at}ottawaheart.ca.
Abstract—Central
infusions of benzamil prevent/reverse salt-induced hypertension in
genetic models of salt-sensitive hypertension. Benzamil acts by
blockade of ion—presumably sodium—channels. In the present study,
we assessed in Dahl salt-sensitive (S) rats on high salt intake whether
these channels mediate increases in brain "ouabain" and, thereby,
hypertension. Intracerebroventricular
(icv) infusions of a low (1.2 µg/kg per hour) or high (4.0
µg/kg per hour) dose of benzamil were given to Dahl S rats on high
salt diet (1370 µmol Na+/g food) for 2 or
4 weeks. "Ouabain" content was measured using a specific
enzyme-linked immunosorbent assay (ELISA). Systolic blood
pressure (BP) in Dahl S rats on high salt for 4 weeks increased
markedly (188±10 versus 128±4 mm Hg, n=8,
P<0.05). Benzamil fully
blocked this increase (131±7 mm Hg after the high dose of
benzamil). Hypothalamic and pituitary "ouabain" increased
significantly (22±7 versus 12±3 and 151±38 versus 69±6 ng/g tissue,
respectively, P<0.05) in Dahl
S rats on high salt versus regular salt diet for 2 weeks. Benzamil
blocked these increases of brain "ouabain" to high salt intake.
Similarly, high salt intake for 4 weeks increased hypothalamic (18±2
versus 13±1 ng/g tissue,
P<0.05) and pituitary (183±30
versus 78±8 ng/g tissue,
P<0.05) "ouabain."
Benzamil also inhibited these increases of brain "ouabain." Both
hypothalamic and pituitary "ouabain" showed significant positive
correlations with BP. In contrast, high salt intake did not affect
"ouabain" levels in the adrenal gland or plasma in Dahl S rats on
high salt for either 2 or 4 weeks. These findings indicate that in Dahl
S rats high salt intake only increases brain and not
peripheral "ouabain" and that benzamil-blockable brain
sodium channels mediate the increases in brain "ouabain" and the
subsequent hypertension.
Accepted on May 8, 2002
Brain Sodium Channels Mediate Increases in Brain
"Ouabain" and Blood Pressure in Dahl S Rats
Hao Wang and Frans H.H. Leenen*
Key words: ouabain • brain • blood pressure • sodium channels
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