Effects of Losartan on Catecholamine Release in the Isolated Rat Adrenal Gland
The Korean Journal of Physiology and Pharmacology
;
: 327-335, 2009.
Artigo
em Inglês
| WPRIM
| ID: wpr-727516
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Veias
/
Veratridina
/
Angiotensina II
/
Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)
/
Cálcio
/
Receptores Nicotínicos
/
Glândulas Suprarrenais
/
Medula Suprarrenal
/
Células Cromafins
/
Losartan
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2009
Tipo de documento:
Artigo
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