Lim D-Y, Jang S-J, Park D-G
Department of Pharmacology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Auton Autacoid Pharmacol. 2002 Aug;22(4):225-32. doi: 10.1046/j.1474-8673.2002.00264.x.
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.
1 本研究旨在调查成年自发性高血压大鼠（SHR）和正常血压的Wistar-Kyoto大鼠（WKYR）离体灌注肾上腺中，胆碱能受体刺激和膜去极化所诱发的儿茶酚胺（CA）分泌情况。2 SHR肾上腺的湿重高于WKYR。WKYR中，乙酰胆碱（5.32×10⁻³ m）和膜去极化剂高钾（5.6×10⁻² m）诱发的CA释放反应显著低于SHR。3 神经元烟碱样受体的选择性激动剂DMPP（10⁻⁴ m，作用2分钟）和神经元毒蕈碱样受体的选择性激动剂McN-A-343（10⁻⁴ m，作用2分钟）诱发的CA分泌反应，WKYR也显著低于SHR。4 二氢吡啶敏感的Ca²⁺通道激活剂Bay-K-8644（10⁻⁵ m）和内质网中Ca²⁺-ATPase的选择性抑制剂环匹阿尼酸（10⁻⁵ m）诱发的CA释放，SHR也显著高于WKYR。5 综上所述，这些实验结果表明，与WKYR相比，SHR灌注肾上腺中胆碱能（烟碱样和毒蕈碱样）受体刺激以及膜去极化所诱发的CA分泌增强更为显著。提示与WKYR相比，SHR中CA释放增加参与了原发性高血压的发病机制。
