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Hypothalamic angiotensin receptor subtypes in normotensive and hypertensive rats
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore 0511 The binding of 125 I-labeled [Sar 1 ,Ile 8 ]angiotensin II to the hypothalamic membranes of the normotensive Wistar-Kyoto rat (WKY) and the spontaneously hypertensive rat (SHR) was studied. Displacement...
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Published in: | American journal of physiology. Heart and circulatory physiology 1998-08, Vol.275 (2), p.H703-H709 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Department of Pharmacology, Faculty of Medicine, National
University of Singapore, Singapore 0511
The binding of
125 I-labeled
[Sar 1 ,Ile 8 ]angiotensin
II to the hypothalamic membranes of the normotensive Wistar-Kyoto rat
(WKY) and the spontaneously hypertensive rat (SHR) was studied.
Displacement experiments with four centrally active angiotensins,
losartan, and PD-123319 confirm the known existence of angiotensin
AT 1 and AT 2 receptors in the rat
hypothalamus. The values of the inhibitory constants for angiotensin II
and PD-123319 in the SHR were significantly lower than the
corresponding values in the WKY, indicating the possible existence of
high-affinity hypothalamic AT 1 and
AT 2 receptors for the two ligands
in the SHR. The angiotensin AT 1
receptor was further separated into a 5'-guanylyl
imidodiphosphate-sensitive and -nonsensitive subtype, indicating that
one of the subtypes is G protein coupled. The SHR has significantly
higher numbers of measurable
AT 1 -receptor subtypes as well as
AT 2 receptor subtypes. The former
data support the findings of other investigators showing that the
hypothalamus of the SHR expressed more
AT 1A and
AT 1B mRNAs than that of the
normotensive rat.
Des-Asp 1 -angiotensin I, which is
known to attenuate the central pressor action of angiotensin II and
angiotensin III, acts on both the AT 1 and
AT 2 receptors, although it has a
higher affinity for the AT 1
receptors. The overall increase in the number of
AT 1 and
AT 2 receptors in the SHR is in
line with the contention that the brain of the hypertensive rat,
compared with that of the WKY, has a hyperactive renin-angiotensin
system.
rat hypothalamus; des-aspartate-angiotensin I; angiotensin
AT 1A receptor; angiotensin
AT 1B receptor |
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ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.1998.275.2.h703 |