AT1 and AT2-receptor antagonists inhibit Ang II-mediated facilitation of noradrenaline release in human atria

Journal of Cardiovascular Pharmacology
Malek El MuayedL C Rump

Abstract

It is generally accepted that regulation of blood pressure and sympathetic neurotransmission by angiotensin (Ang) II is brought about through activation of AT1-receptors. Since recent studies demonstrated a high proportion of AT2-receptors in the human heart, the aim of our study was to investigate whether Ang II modulates noradrenaline release also through activation of AT2-receptors in this tissue. Human atrial appendages were prelabeled with [3H]-noradrenaline and electrically field-stimulated. Stimulation-induced outflow of radioactivity was taken as an index of endogenous noradrenaline release. Ang I and II enhanced noradrenaline release in a dose-dependent manner up to 55 and 72%, respectively. These effects were blocked by the selective AT1-receptor antagonists EXP3174 and irbesartan (10 nmol/L). Moreover, the selective AT2-receptor antagonists PD123319 and CGP42112A (0.1 and 1 micromol/L) also inhibited Ang II-induced facilitation of noradrenaline release. Captopril (5 micromol/L) shifted the dose response curve for Ang I less potent to the right than EXP3174 (10 nmol/L). Ang I and II enhanced the stimulation-induced noradrenaline release significantly more potent in tissues of patients pretreated with ACE inhibitors th...Continue Reading

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Citations

Sep 28, 2004·Naunyn-Schmiedeberg's Archives of Pharmacology·Serafim GuimarãesDaniel Moura
Aug 12, 2005·Journal of Hypertension·Johannes StegbauerLars Christian Rump
Aug 2, 2008·Journal of Cardiovascular Pharmacology·Tetsumasa SasaokaYasuo Matsumura
Oct 7, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Mirnela BykuThomas C Westfall
Jul 16, 2011·Regulatory Peptides·S A PotthoffO Vonend
Oct 12, 2010·Journal of Molecular and Cellular Cardiology·Neil HerringDavid J Paterson
Jul 22, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Niwanthi W RajapakseRoger G Evans
May 8, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Fumiko YamakiYoshio Tanaka

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