TY - JOUR
T1 - Differential blockade of central effects of angiotensin II by AT2- receptor antagonists
AU - Widdop, R. E.
AU - Gardiner, S. M.
AU - Kemp, P. A.
AU - Bennett, T.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - In conscious, chronically instrumented, male Long-Evans rats, we showed previously that central administration (intracerebroventricular) of the AT1- receptor antagonist EXP-3174 (1 μg) caused a rapid-onset marked, but transient, blockade of the regional hemodynamic responses to intracerebroventricular angiotensin II (ANG II). In contrast, the AT2- receptor antagonist PD-123319 (80 μg) caused a slow-onset, but marked and persistent, antagonism of the effects of intracerebroventricular ANG II. In the present study we attempted to mimic the actions of PD-123319 by giving a supramaximal dose of EXP-3174 (10 μg), and we also assessed the effects of PD-123177 (80 μg), an AT2-receptor antagonist that differs from PD-123319 only by a dimethyl group. The higher dose of EXP-3174 did not exert prolonged antagonistic effects against responses to intracerebroventricular ANG II, and PD-123177 was without inhibitory effects in this model. The results indicate important functional differences between putative AT2-receptor antagonists, when assessed in vivo, that are not apparent from binding studies.
AB - In conscious, chronically instrumented, male Long-Evans rats, we showed previously that central administration (intracerebroventricular) of the AT1- receptor antagonist EXP-3174 (1 μg) caused a rapid-onset marked, but transient, blockade of the regional hemodynamic responses to intracerebroventricular angiotensin II (ANG II). In contrast, the AT2- receptor antagonist PD-123319 (80 μg) caused a slow-onset, but marked and persistent, antagonism of the effects of intracerebroventricular ANG II. In the present study we attempted to mimic the actions of PD-123319 by giving a supramaximal dose of EXP-3174 (10 μg), and we also assessed the effects of PD-123177 (80 μg), an AT2-receptor antagonist that differs from PD-123319 only by a dimethyl group. The higher dose of EXP-3174 did not exert prolonged antagonistic effects against responses to intracerebroventricular ANG II, and PD-123177 was without inhibitory effects in this model. The results indicate important functional differences between putative AT2-receptor antagonists, when assessed in vivo, that are not apparent from binding studies.
KW - AT and AT receptors
KW - central cardiovascular control
UR - http://www.scopus.com/inward/record.url?scp=0027293303&partnerID=8YFLogxK
M3 - Article
C2 - 8342637
AN - SCOPUS:0027293303
SN - 0363-6135
VL - 265
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 1 34-1
ER -