The role of paraventricular angiotensin at-1 receptors in salt
sensitive hypertension in mren-2 transgenic rats.
Li, Ping, Mariana Morris, Debra I. Diz, Carlos M. Ferrario, Detlev
Ganten, and Michael F. Callahan.
Departments of Physiology and Pharmacology and the Hypertension
Center, Bowman Gray School of Medicine of Wake Forest University,
Winston-Salem, NC 27157 and Max Delbruck Center for Molecular
Medicine, Berlin-Buch, Germany
APStracts 3:0073R, 1996.
We have previously demonstrated that mRen-2 transgenic [Tg(+)] rats
show a salt-induced exacerbation of hypertension (5). In this study,
we examined the role of paraventricular (PVN) angiotensin type-1 (AT
-1) receptors in the salt sensitivity of this model. Male Tg(+) and
Tg(-) rats were instrumented with PVN cannulae for intracerebral drug
administration and carotid catheters for chronic cardiovascular
monitoring. Substitution of 2% NaCl for drinking water for four days
caused a significant elevation (23 mmHg) of mean arterial pressure
(MAP) in Tg(+) rats but not in Tg(-) rat. PVN injection of AT-1
receptor antisense oligodeoxynucleotides (ASODN), but not scrambled
oligodeoxynucleotides (SCODN), produced a rapid decrease in mean
arterial pressure (MAP) of 24+/-8 mmHg in salt-treated Tg (+) rats.
There was no effect of either AT-1 ASODN or SCODN on MAP in salt
loaded Tg(-) rats or in Tg(+) rats consuming tap water. Salt loading
significantly increased subfornical organ (SFO) AT-1 receptors in
Tg(+) rats with no changes produced by ASODN or SCODN. In contrast,
there was a 40% decrease in PVN AT-1 receptors 20 hours after the
direct PVN injection of AT-1 ASODN injection, compared with SCODN in
Tg(+) rats. We conclude that PVN AT-1 receptors are critical in the
expression of salt sensitivity in mRen-2 transgenic rats.
Received 18 December 1995; accepted in final form 22 February
1996.
APS Manuscript Number R801-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96