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(Hypertension. 1998;32:1028-1033.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Both Brain Angiotensin II and "Ouabain" Contribute to Sympathoexcitation and Hypertension in Dahl S Rats on High Salt Intake
From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Correspondence to Frans H.H. Leenen, MD, PhD, FRCPC, Hypertension Unit, H360, Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin St, Ottawa, Ontario K1Y 4W7, Canada. E-mail fleenen{at}ohi-net.heartinst.on.ca
Abstract—Dahl salt-sensitive
(Dahl S) and salt-resistant (Dahl R) rats from 5 to 9 weeks of
age received a regular or high salt diet and concomitantly an
intracerebroventricular infusion of the
angiotensin type 1 blocker losartan (1 mg ·
kg-1 · d-1) or antibody Fab fragments,
which bind ouabain and related steroids with high affinity, or
-globulins as control (200 µg/d for both). At 9 weeks of age,
blood pressure (BP), heart rate (HR), central venous pressure, and
renal sympathetic nerve activity were recorded in conscious rats at
rest and in response to air stress and to
intracerebroventricular
2-agonist guanabenz (50 µg) and ouabain (0.5 µg).
Baroreflex function was assessed by acute volume expansion with
intravenous 5% dextrose and ramp changes of BP by
±50 mm Hg induced by intravenous
phenylephrine and sodium nitroprusside. In Dahl S but not R
rats, high salt significantly increased BP and HR; enhanced BP, HR, and
renal sympathetic nerve activity responses to air stress and guanabenz;
and attenuated cardiopulmonary and arterial
baroreflex control of renal sympathetic nerve activity and HR. Both
losartan and Fab fragments prevented these responses to high
salt to a similar extent in Dahl S rats but had no effect in Dahl R
rats on high salt. Sympathoexcitatory responses
to ouabain were attenuated in Dahl S on high versus regular salt and
were abolished in Dahl R or S treated with losartan or Fab
fragments. Consistent with previous studies in SHR, the
present data indicate that in Dahl S on high salt, both brain
"ouabain" and angiotensin II contribute to decreased
sympathoinhibition and increased sympathoexcitation, impairment of
baroreflex, and therefore hypertension.
Key Words: sympathetic nervous system • baroreflex • losartan • stress • guanabenz • antibody Fab fragments
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