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1 The present study was designed to investigate the secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused adrenal gland of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKYR) at adult age. 2 The wet weight of adrenal gland in SHR was greater than that in WKYR. The CA releasing responses evoked by acetylcholine (5.32 x 10-3 m), and high potassium (5.6 x 10-2 m), a membrane depolarizer, were significantly lower in WKYR than in SHR. 3 The secretory responses of CA evoked by DMPP (10-4 m for 2 min), a selective agonist of neuronal nicotinic receptors, and McN-A-343 (10-4 m for 2 min), a selective agonist of neuronal muscarinic receptors, were also significantly lower in WKYR than in SHR. 4 The CA release evoked by Bay-K-8644 (10-5 m), a dihydropyridine-sensitive Ca2+ channel activator, and cyclopiazonic acid (10-5 m), a selective inhibitor of Ca2+-ATPase in the endoplasmic reticulum, were also significantly greater in SHR than WKYR. 5 Taken together, these experimental results demonstrate that the CA secretion evoked by stimulation of cholinergic (nicotinic and muscarinic) receptors as well as membrane depolarization is enhanced more greatly in the perfused adrenal glands of SHR than in those of WKYR. It is suggested that the augmented CA release in SHR compared with WKYR was involved in essential hypertensive pathogenesis.

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 μg/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 μg/mL) also time-dependently inhibited the CA secretion evoked by 1.1-dimethyl-4 -phenyl piperazinium iodide (DMPP; 100 μM, a selective neuronal nicotinic receptor agonist) and McN-A-343 (100 μM, a selective muscarinic M1 receptor agonist). TGS itself did not affect basal CA secretion (data not shown). Also, in the presence of TGS (50 μg/mL), the secretory responses of CA evoked by veratridine (a selective Na+ channel activator (50 μM), Bay-K-8644 (an L-type dihydropyridine Ca2+ channel activator, 10 μM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 μM) were significantly reduced, respectively. Interestingly, in the simultaneous presence of TGS (50 μg/mL) and Nω-nitro-L-arginine methyl ester hydrochloride [an inhibitor of nitric oxide (NO) synthase, 30 μM], 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 μg/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 Ca2+ and Na+ into the adrenomedullary chromaffin cells and also by suppressing the release of Ca2+ 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.

Aim: To study the effect of arecoline, an alkaloid isolated from Areca catechu, on the secretion of catecholamines (CA) evoked by cholinergic agonists and the membrane depolarizer from isolated perfused rat adrenal gland. Methods: Adrenal glands were isolated from male Sprague‐Dawley rats. The adrenal glands were perfused with Krebs bicarbonate solution by means of a peristaltic pump. The CA content of the perfusate was measured directly using the fluorometric method. Results: Arecoline (0.1–1.0 mmol/L) perfused into an adrenal vein for 60 min produced dose‐ and time‐dependent inhibition in CA secretory responses evoked by acetylcholine (ACh) (5.32 mmol/L), 1.1‐dimethyl‐4‐phenyl piperazinium iodide (DMPP) (100 μmol/L for 2 min) and 3‐(m‐choloro‐phenyl‐carbamoyl‐oxy)‐2‐butynyl trimethyl ammonium chloride (McN‐A‐343) (100 μmol/L for 2 min). However, lower doses of arecoline did not affect CA secretion of high K+ (56 mmol/L); higher doses greatly reduced CA secretion of high K+. Arecoline also failed to affect basal catecholamine output. Furthermore, in adrenal glands loaded with arecoline (0.3 mmol/L), CA secretory response evoked by Bay‐K‐8644 (10 μmol/L), an activator of L‐type Ca2+ channels, was markedly inhibited, whereas CA secretion by cyclopiazonic acid (10 μmol/L), an inhibitor of cytoplasmic Ca2+‐ATPase, was not affected. Nicotine (30 μmol/L), which was perfused into the adrenal gland for 60 min, however, initially enhanced ACh‐evoked CA secretory responses. As time elapsed, these responses became more inhibited, whereas the initially enhanced high K+‐evoked CA release diminished. CA secretion evoked by DMPP and McN‐A‐343 was significantly depressed in the presence of nicotine. Conclusion: Arecoline dose‐dependently inhibits CA secretion from isolated perfused rat adrenal gland evoked by activation of cholinergic receptors. At lower doses arecoline does not inhibit CA secretion through membrane depolarization, but at larger doses it does. This inhibitory effect of arecoline may be mediated by blocking the calcium influx into the rat adrenal medullary chromaffin cells without the inhibition of Ca2+ release from the cytoplasmic calcium store. There seems to be a difference in the mode of action of nicotine and arecoline in rat adrenomedullary CA secretion.

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The aim of the present study was to investigate whether polyphenolic compounds isolated from wine brewed from Rubus coreanum MIQUEL (PCRC) may affect the release of catecholamine (CA) from the isolated perfused rat adrenal medulla, and to establish its mechanism of action. PCRC (20-180 microg/mL) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory responses evoked by acetylcholine (ACh, 5.32 mM), high K+ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic Nn receptor agonist, 100 microM) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100 microM). Also, in the presence of PCRC (60 microg/mL), the secretory responses of CA evoked by Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 microM) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 microg/mL) and L-NAME (an inhibitor of NO synthase, 30 microM), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of PCRC alone. Taken together, these results obtained from the present study demonstrate that PCRC inhibits the CA secretory responses from the isolated perfused adrenal gland of the normotensive rats evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is exerted by inhibiting both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the cytoplasmic calcium store partly through the increased NO production due to the activation of nitric oxide synthase (NOS), which are at least relevant to the direct interaction with the nicotinic receptor itself. It is also thought that PCRC might be effective in prevention of cardiovascular disease.