TY - JOUR
T1 - Properly timed exposure to central ANG II prevents behavioral sensitization and changes in angiotensin receptor expression
AU - Santollo, Jessica
AU - Whalen, Philip E.
AU - Speth, Robert C.
AU - Clark, Stewart D.
AU - Daniels, Derek
N1 - Publisher Copyright:
© 2014 the American Physiological Society.
PY - 2014/12/15
Y1 - 2014/12/15
N2 - Previous studies show that the angiotensin type 1 receptor (AT1R) is susceptible to rapid desensitization, but that more chronic treatments that stimulate ANG II lead to sensitization of several responses. It is unclear, however, if the processes of desensitization and sensitization interact. To test for differences in AT1R expression associated with single or repeated injections of ANG II, we measured AT1R mRNA in nuclei that control fluid intake of rats given ANG II either in a single injection or divided into three injections spaced 20 min apart. Rats given a single injection of ANG II had more AT1R mRNA in the subfornical organ (SFO) and the periventricular tissue surrounding the anteroventral third ventricle (AV3V) than did controls. The effect was not observed, however, when the same cumulative dose of ANG II was divided into multiple injections. Behavioral tests found that single daily injections of ANG II sensitized the dipsogenic response to ANG II, but a daily regimen of four injections did not cause sensitization. Analysis of 125I-Sar1-ANG II binding revealed a paradoxical decrease in binding in the caudal AV3V and dorsal median preoptic nucleus after 5 days of single daily injections of ANG II; however, this effect was absent in rats treated for 5 days with four daily ANG II injections. Taken together, these data suggest that a desensitizing treatment regimen prevents behaviorand receptor-level effects of repeated daily ANG II.
AB - Previous studies show that the angiotensin type 1 receptor (AT1R) is susceptible to rapid desensitization, but that more chronic treatments that stimulate ANG II lead to sensitization of several responses. It is unclear, however, if the processes of desensitization and sensitization interact. To test for differences in AT1R expression associated with single or repeated injections of ANG II, we measured AT1R mRNA in nuclei that control fluid intake of rats given ANG II either in a single injection or divided into three injections spaced 20 min apart. Rats given a single injection of ANG II had more AT1R mRNA in the subfornical organ (SFO) and the periventricular tissue surrounding the anteroventral third ventricle (AV3V) than did controls. The effect was not observed, however, when the same cumulative dose of ANG II was divided into multiple injections. Behavioral tests found that single daily injections of ANG II sensitized the dipsogenic response to ANG II, but a daily regimen of four injections did not cause sensitization. Analysis of 125I-Sar1-ANG II binding revealed a paradoxical decrease in binding in the caudal AV3V and dorsal median preoptic nucleus after 5 days of single daily injections of ANG II; however, this effect was absent in rats treated for 5 days with four daily ANG II injections. Taken together, these data suggest that a desensitizing treatment regimen prevents behaviorand receptor-level effects of repeated daily ANG II.
KW - AT1R
KW - Drinking microstructure
KW - Fluid balance
KW - Water intake
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U2 - 10.1152/ajpregu.00373.2014
DO - 10.1152/ajpregu.00373.2014
M3 - Article
C2 - 25354729
AN - SCOPUS:84919459354
SN - 0363-6119
VL - 307
SP - R1396-R1404
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 12
ER -