Differential blockade of central effects of angiotensin II by AT2- receptor antagonists

R. E. Widdop, S. M. Gardiner, P. A. Kemp, T. Bennett

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Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume265
Issue number1 34-1
Publication statusPublished - 1 Jan 1993

Keywords

  • AT and AT receptors
  • central cardiovascular control

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