Influence of PD 123319 (AT 2 -Receptor Antagonist) on Catecholamine Secretion in the Perfused Rat Adrenal Medulla (original) (raw)

2013, Journal of the Korean Society of Hypertension

Background: The aim of this study was to examine whether PD 123319 (an angiotensin II type 2 [AT 2 ] receptor antagonist) can influence the release of catecholamines (CA) from the perfused model of the rat adrenal medulla. Methods: The adrenal gland was isolated by the modification of Wakade method, and perfused with normal Krebs-bicarbonate solution. The content of CA was measured using the fluorospectrophotometer. Results: During perfusion of PD 123319 (range, 5 to 50 nM) into an adrenal vein for 90 minutes the CA secretory responses evoked by acetylcholine (ACh), high K + , 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), and McN-A-343 was dose-and time-dependently inhibited. Furthermore, loading with PD 123319 for 90 minutes also markedly inhibited the CA secretory responses evoked by 4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644), cyclopiazonic acid, veratridine, and angiotensin II (Ang II). PD 123319 did not affect basal CA output. Simultaneous perfusion of PD 123319 and CGP 42112 perfused into an adrenal vein for 90 minutes rather more potently inhibited the CA seretory responses evoked by Ach, high K+, DMPP, Bay-K-8644, veratridine, and Ang II compared to the inhibitory effect by PD123319-treated alone. Conclusions: Taken together, these results show that PD 123319 inhibits the CA secretion evoked by both cholinergic and Ang II receptor stimulation from the perfused rat adrenal medulla. This inhibitory effect of PD 123319 seems to be exerted by blocking the influx of both Na + and Ca 2+ through their voltage-dependent channels into the rat adrenomedullary chromaffin cells as well as by reducing the Ca 2+ release from its cytoplasmic calcium store, which may be relevant to AT 2 receptor blockade. Based on these present data, it is thought that PD 123319 has different activity from previously known AT 2 antagonist activity in the perfused adrenal medulla, and that AT 2 receptors may be involved in the rat adrenomedullary CA secretion.