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In vivo analysis of brain AT1 angiotensin receptor signaling pathways
Author(s) -
Karamyan Vardan T.,
Speth Robert C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a792-c
Subject(s) - chelerythrine , angiotensin ii , endocrinology , medicine , protein kinase c , angiotensin ii receptor type 1 , chemistry , kinase , receptor , protein kinase a , phospholipase c , renin–angiotensin system , pharmacology , blood pressure , biochemistry
AT1 receptors mediate pressor and dipsogenic actions of angiotensin II (Ang II) in the brain. This study examined intracellular signaling pathways of brain AT1 receptors in vivo , using specific inhibitors and Ang II, administered intracerebroventricularly. Vehicle or inhibitor (2 μl) was given 15 min prior to Ang II (100 pmol/2 μl artificial CSF) to adult, male Sprague‐Dawley rats implanted with radiotelemetric blood pressure transducers. Increases in mean arterial blood pressure (BP) and volume of water drunk (WV) in response to Ang II were monitored. U‐73122 (2 nmol) a phospholipase C inhibitor, but not the inactive analog U‐73433 (n=4), attenuated the effects of Ang II (BP: 41.7 %; WV: 56.5 %; p<0.05 n = 6). Chelerythrine (100 pmol) a protein kinase C (PKC) inhibitor also inhibited the Ang II effects (BP: 20.1% p<0.01; WV: 37.5% p<0.05 n=8). PD‐98059 (1 nmol) an MAP kinase kinase (MEK, ERK/MAP kinase cascade) inhibitor attenuated only the Ang II pressor effect (28.2% p<0.05 n=6). Neither KN‐93 (40 pmol, n=6) a Ca 2+ /Calmodulin‐kinase II (CaCMK II) inhibitor nor wortmannin (40 pmol, n=5) a PI 3 ‐kinase inhibitor affected the Ang II responses. The results indicate that the PLC/PKC pathway is the dominant mediator of brain AT1 responses. The differential effects of the MEK inhibitor on pressor and dipsogenic responses suggests that the MAPK cascade may mediate pressor, but not dipsogenic effects of Ang II in the brain.