• The Korean Journal of Physiology and Pharmacology
• /
• 제14권4호
• /
• pp.241-248
• /
• 2010

The present sutdy aimed to determine whether olmesartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor blocker, can influence the CA release from the isolated perfused model of the rat adrenal medulla. Olmesartan ($5{\sim}50{\mu}M$) 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 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Olmesartan did not affect basal CA secretion. Also, in adrenal glands loaded with olmesartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of voltage-dependent L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), veratridine (100 ${\mu}M$, an activator of voltage-dependent $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations ($150{\sim}300{\mu}M$), 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 $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement on the CA secreton.

• Journal of Ginseng Research
• /
• 제35권2호
• /
• pp.176-190
• /
• 2011

There seems to be some controversy about the effect of total ginseng saponin (TGS) on the secretion of catecholamines (CA) from the adrenal gland. Therefore, the present study aimed to determine whether TGS can affect the CA release in the perfused model of the adrenal medulla isolated from spontaneously hypertensive rats (SHRs). TGS (15-150 ${\mu}g/mL$), perfused into an adrenal vein for 90 min, inhibited the CA secretory responses evoked by acetylcholine (ACh, 5.32 mM) and high $K^+$ (56 mM, a direct membrane depolarizer) in a dose- and time-dependent fashion. TGS (50 ${\mu}g/mL$) also time-dependently inhibited the CA secretion evoked by 1.1-dimethyl-4 -phenyl piperazinium iodide (DMPP; 100 ${\mu}M$, a selective neuronal nicotinic receptor agonist) and McN-A-343 (100 ${\mu}M$, a selective muscarinic M1 receptor agonist). TGS itself did not affect basal CA secretion (data not shown). Also, in the presence of TGS (50 ${\mu}g/mL$), the secretory responses of CA evoked by veratridine (a selective $Na^+$ channel activator (50 ${\mu}M$), Bay-K-8644 (an L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}M$) were significantly reduced, respectively. Interestingly, in the simultaneous presence of TGS (50 ${\mu}g/mL$) and N${\omega}$-nitro-L-arginine methyl ester hydrochloride [an inhibitor of nitric oxide (NO) synthase, 30 ${\mu}M$], the inhibitory responses of TGS on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid, and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of TGS-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of TGS (150 ${\mu}g/mL$) was greatly elevated compared to the corresponding basal released level. Taken together, these results demonstrate that TGS inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the isolated perfused adrenal medulla of the SHRs. It seems that this inhibitory effect of TGS is mediated by inhibiting both the influx of $Ca^{2+}$ and Na+ into the adrenomedullary chromaffin cells and also by suppressing the release of $Ca^{2+}$ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade, without the enhancement effect on the CA release. Based on these effects, it is also thought that there are some species differences in the adrenomedullary CA secretion between the rabbit and SHR.

• The Korean Journal of Physiology and Pharmacology
• /
• 제11권1호
• /
• pp.21-30
• /
• 2007

The present study was designed to establish comparatively the inhibitory effects of cilnidipine(CNP), nifedipine(NIF), and $\omega$-conotoxin GVIA(CTX) on the release of CA evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. CNP(3 ${\mu}M$), NIF(3 ${\mu}M$), and CTX(3 ${\mu}M$) perfused into an adrenal vein for 60 min produced greatly inhibition in CA secretory responses evoked by ACh($5.32{\times}10^{-3}M$), DMPP($10^{-4}M$ for 2 min), McN-A-343($10^{-4}M$ for 2 min), high $K^+(5.6{\times}10^{-2}M)$, Bay-K-8644($10^{-5}M$), and cyclopiazonic acid($10^{-5}M$), respectively. For the CA release evoked by ACh and Bay-K-8644, the following rank order of potency was obtained: CNP>NIF>CTX. The rank order for the CA release evoked by McN-A-343 and cyclopiazonic acid was CNP>NIF>CTX. Also, the rank orders for high $K^+$ and for DMPP were NIF>CTX>CNP and NIF>CNP>CTX, respectively. Taken together, these results demonstrate that all voltage-dependent $Ca^{2+}$ channels(VDCCs) blockers of cilnidipine, nifedipine, and $\omega$-conotoxin GVIA inhibit greatly the CA release evoked by stimulation of cholinergic(both nicotinic and muscarinic) receptors and the membrane depolarization without affecting the basal release from the isolated perfused rat adrenal gland. It seems likely that the inhibitory effects of cilnidipine, nifedipine, and $\omega$-conotoxin GVIA are mediated by the blockade of both L- and N-type, L-type only, and N-type only VDCCs located on the rat adrenomedullary chromaffin cells, respectively, which are relevant to $Ca^{2+}$ mobilization. It is also suggested that N-type VDCCs play an important role in the rat adrenomedullary CA secretion, in addition to L-type VDCCs.

• 대한약리학회지
• /
• 제26권2호
• /
• pp.101-111
• /
• 1990

흰쥐, 개, 고양이의 뇌내의 머스커린수용체에 작용함이 알려져 있는 physostigmine(PS)의 동맥혈압에 미치는 효과를 urethane마취토끼에서 조사하였다. 정맥내 (iv) PS $25{\sim}250{\mu}g/kg$은 혈압변동을 일으키지 않았다. 그러나 토끼를 chlorisondamine(CS), hexamethonium, 뇌실내 (icv) clonidine, icv xylazine, icv reserpine으로 처리후 또는 척수이단후에는 승압반응을 일으켰다. CS처리토끼의 iv PS승압반응은 prazosin또는 pirenzepine처리후에는 현저히 약화되었다. Iv PS는 CS처리나 척수이단토끼에서 일어나는 McN-A-343의 승압효과를 억제하였고 또 McN-A-343주입시에는 iv PS는 승압을 일으키지 않았다. DMPP의 승압효과는 iv PS의 영향을 받지 않았다. Icv PS $12{\sim}100{\mu}g/kg$은 승압반응을 일으켰고 이는 CS처리로 강화되었다. 이 승압효과는 완전치는 않으나 prazosin 또는 pirenzepine으로 억제되었다. Angiotensin II 길항약인 $(Sar^{1},\;Ala^{8})-angiotensin$ II와 prazosin또는 pirenzepine으로 토끼를 처리할때는 icv PS승압효과는 거의 볼 수 없었다. 그러나 이 angiotensin II 길항약은 prazosin, pirenzepine의 iv PS승압반응에 대한 억제효과는 항진시키지 않았다. Icv pirenzepine은 icv PS승압반응은 차단하였으나, iv PS승압효과에는 영향을 미치지 않았다. 본실험성적은 CS처리 및 척수이단토끼에서 볼 수 있는 iv PS승압은 교감신경절의 머스커린수용체의 흥분으로 일어나고, icv PS승압은 뇌내의 머스커린수용체의 흥분으로 교감신경계 및 angiotensin계의 활성도가 높아져서 일어남을 가리키고 있다. 또한 토끼에서는 교감신경절니코틴수용체차단, 교감신경절에 미치는 중추 교감신경의 지배력의 감소 또는 척수이단등으로 교감신경절 머스커린수응체의 감수성이 바꾸어지지 않은한 iv PS는 승압반응을 일으키지 못함을 시사하고 있다.