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KMID : 0811720100140040241
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Korean Journal of Physiology & Pharmacology
2010 Volume.14 No. 4 p.241 ~ p.248
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Inhibitory Effects of Olmesartan on Catecholamine Secretion from the Perfused Rat Adrenal Medulla
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Lim Hyo-Jeong
Kim Sang-Yong
Lim Dong-Yoon
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Abstract
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The present sutdy aimed to determine whether olmesartan, an angiotensin II (Ang II) type 1 (AT1) receptor blocker, can influence the CA release from the isolated perfused model of the rat adrenal medulla. Olmesartan (5∼50?M) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high K＋ (56 mM, a direct membrane-depolarizer), DMPP (100?M) and McN-A-343 (100?M). Olmesartan did not affect basal CA secretion. Also, in adrenal glands loaded with olmesartan (15?M), the CA secretory responses evoked by Bay-K-8644 (10?M, an activator of voltage-dependent L-type Ca2＋ channels), cyclopiazonic acid (10?M, an inhibitor of cytoplasmic Ca2＋-ATPase), veratridine (100?M, an activator of voltage-dependent Na＋ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations (150∼300?M), olmesartan rather enhanced the ACh-evoked CA secretion. Taken together, these results show that olmesartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by direct membrane depolarization from the rat adrenal medulla, but at high concentrations it rather potentiates the ACh-evoked CA secretion. It seems that olmesartan has a dual action, acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of olmesartan may be mediated by blocking the influx of both Na＋ and Ca2＋ into the rat adrenomedullary chromaffin cells as well as by inhibiting the Ca2＋ release from the cytoplasmic calcium store, which is thought to be relevant to the AT1 receptor blockade, in addition to its enhancement on the CA secreton.
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KEYWORD
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Olmesartan, Catecholamine secretion, Adrenal medulla, AT1 receptor blockade
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