Effects of Losartan on Catecholamine Release in the Isolated Rat Adrenal Gland.
10.4196/kjpp.2009.13.4.327
- Author:
Hae Jeong NOH
1
;
Yoon Sung KANG
;
Dong Yoon LIM
Author Information
1. Department of Family Medicine, Eulji University Hospital, Daejeon 302-799,.
- Publication Type:Original Article
- Keywords:
Losartan;
Catecholamine Release;
Adrenal Medulla;
AT1 receptor blockade
- MeSH:
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride;
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester;
Adrenal Glands;
Adrenal Medulla;
Angiotensin II;
Animals;
Calcium;
Chromaffin Cells;
Cytoplasm;
Dimethylphenylpiperazinium Iodide;
Indoles;
Losartan;
Membranes;
Rats;
Receptors, Nicotinic;
Veins;
Veratridine
- From:The Korean Journal of Physiology and Pharmacology
2009;13(4):327-335
- CountryRepublic of Korea
- Language:English
-
Abstract:
The aim of this study was to determine whether losartan, an angiotensin II (Ang II) type 1 (AT1) receptor could influence the CA release from the isolated perfused model of the rat adrenal medulla. Losartan (5~50 micrometer) 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 micrometer) and McN-A-343 (100 micrometer). Losartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with losartan (15 micrometer) for 90 min, the CA secretory responses evoked by Bay-K-8644 (10 micrometer, an activator of L-type Ca2+ channels), cyclopiazonic acid (10 micrometer, an inhibitor of cytoplasmic Ca2+-ATPase), veratridine (100 micrometer, an activator of Na+ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations (150~300 micrometer), losartan rather enhanced the CA secretion evoked by ACh. Collectively, these experimental results suggest that losartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla, but at high concentration it rather inhibits ACh-evoked CA secretion. It seems that losartan has a dual action, acting as both agonist and antagonist to nicotinic receptors of the rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of losartan 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 of the CA release.
