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1 Department of Clinical and
Laboratory Medicine,
To determine the possible involvement of
brain amiloride-sensitive Na+
channels in Na+-induced
hypertension, we investigated the effects of benzamil hydrochloride, a
specific blocker of these Na+
channels, on the acute pressor mechanisms of intracerebroventricular infusion of hypertonic NaCl and the continuous pressor mechanisms of
Na+-induced chronic hypertension,
such as deoxycorticosterone acetate-salt hypertensive or stroke-prone
spontaneous hypertensive rats, and of
non-Na+-induced hypertension, such
as renovascular hypertensive rats. Intracerebroventricular preinjection
with benzamil (1 or 10 nmol/kg) abolished the increase in mean arterial
pressure, heart rate, abdominal sympathetic discharge, and plasma
vasopressin concentration induced by an acute increase in cerebrospinal
Na+ concentrations at
intracerebroventricular infusion of 1.5 M hypertonic NaCl. Continuous
intracerebroventricular infusion of benzamil (1 or 10 nmol · kg
1 · day
1)
for 7 days attenuated Na+-induced
chronic hypertension in both deoxycorticosterone acetate-salt and
stroke-prone spontaneous hypertensive rats, accompanied by reduction of
urinary excretion of vasopressin and norepinephrine but not in
renovascular hypertensive rats. Intravenous infusion of benzamil (10 nmol · kg
1 · day
1)
for 7 days affected neither arterial pressure nor urinary excretion of
vasopressin and norepinephrine in either model of hypertension. Benzamil-blockable brain amiloride-sensitive
Na+ channels are expected to
function as one of the Na+
receptors in the brain and to be involved in the pressor mechanism of
Na+-induced hypertension.
amiloride-sensitive sodium ion channels; deoxycorticosterone acetate-salt; stroke-prone spontaneously hypertensive rat; aortic ligation; sympathetic nervous system; arginine vasopressin
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