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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
Main Authors: Han, N. L, Sim, M. K
Format: Article
Language:English
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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
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.1998.275.2.h703