Department of Anesthesiology and Pain Medicine, Chosun University, Gwangju 501-759, Korea.
Korean J Physiol Pharmacol. 2009 Dec;13(6):517-26. doi: 10.4196/kjpp.2009.13.6.517. Epub 2009 Dec 31.
The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC (20~180 microg/ml) perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high K(+) (56 mM), DMPP (100 microM) and McN-A-343 (100 microM). PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC (60 microg/ml), the CA secretory responses to veratridine (a selective Na(+) channel activator (10 microM), Bay-K-8644 (a L-type dihydropyridine Ca(2+) channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca(2+) -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 that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC (60 microg/ml) was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of Ca(2+) release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.
本研究试图探讨从覆盆子（Rubus coreanum Miquel）酿造的葡萄酒中分离得到的多酚化合物（PCRC）是否会影响自发性高血压大鼠（SHR）离体灌流肾上腺髓质中儿茶酚胺（CA）的释放，并确定其作用机制。PCRC（20~180μg/ml）经肾上腺静脉灌注 90min，相对剂量依赖性地抑制 ACh（5.32mM）、高 K+（56mM）、DMPP（100μM）和 McN-A-343（100μM）刺激引起的 CA 分泌反应。PCRC 本身不影响基础 CA 分泌（未显示数据）。此外，在存在 PCRC（60μg/ml）的情况下，veratridine（一种选择性 Na+通道激活剂（10μM）、Bay-K-8644（一种 L 型二氢吡啶 Ca2+通道激活剂，10μM）和环匹阿尼酸（一种细胞质 Ca2+-ATPase 抑制剂，10μM）引起的 CA 分泌反应明显减少。在同时存在 PCRC（60μg/ml）和 L-NAME（一种一氧化氮合酶抑制剂，30μM）的情况下，与单独使用 PCRC 处理相比，PCRC 对 ACh、高 K+、DMPP 和 Bay-K-8644 引起的 CA 分泌的抑制反应显著恢复到相应对照分泌的程度。与相应的基础水平相比，PCRC（60μg/ml）处理后肾上腺髓质释放的 NO 水平大大升高。总之，这些结果表明，PCRC 抑制 SHR 离体灌流肾上腺髓质中由胆碱能受体刺激以及直接去极化引起的 CA 分泌。这种 PCRC 的抑制作用似乎是通过阻断 Ca2+和 Na+流入 SHR 肾上腺髓质嗜铬细胞以及通过抑制细胞质钙库中的 Ca2+释放来实现的，至少部分是通过激活一氧化氮合酶导致 NO 产生增加。
