Characteristics of ACh-induced hyperpolarization and relaxation in rabbit jugular vein

被引:8
|
作者
Itoh, Takeo [1 ]
Maekawa, Takashi [1 ,2 ]
Shibayama, Yasushi [1 ]
机构
[1] Nagoya City Univ, Dept Pharmacol, Grad Sch Med Sci, Nagoya, Aichi 4678601, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Surg, Div Vasc Surg, Nagoya, Aichi 4648601, Japan
基金
日本学术振兴会;
关键词
ACh; basal NO release; calcium-activated K plus channels; endothelial cell hyperpolarization; EDHF; endothelium; NO; rabbit jugular vein; smooth muscle cell hyperpolarization; voltage-dependent K plus channels; ENDOTHELIUM-DEPENDENT RELAXATION; ACTIVATED POTASSIUM CHANNELS; CA2+-ACTIVATED K+ CHANNEL; NITRIC-OXIDE PRODUCTION; PIG CORONARY-ARTERY; MECHANICAL ACTIVITIES; BLOOD-PRESSURE; L-ARGININE; RAT AORTA; ACETYLCHOLINE;
D O I
10.1111/j.1476-5381.2012.02038.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
BACKGROUND AND PURPOSE The roles played by endothelium-derived NO and prostacyclin and by endothelial cell hyperpolarization in ACh-induced relaxation have been well characterized in arteries. However, the mechanisms underlying ACh-induced relaxation in veins remain to be fully clarified. EXPERIMENTAL APPROACH ACh-induced smooth muscle cell (SMC) hyperpolarization and relaxation were measured in endothelium-intact and -denuded preparations of rabbit jugular vein. KEY RESULTS In endothelium-intact preparations, ACh (=10-8 M) marginally increased the intracellular concentration of Ca2+ ([Ca2+]i) in endothelial cells but did not alter the SMC membrane potential. However, ACh (10-1010-8 M) induced a concentration-dependent relaxation during the contraction induced by PGF2a and this relaxation was blocked by the NO synthase inhibitor N?-nitro-l-arginine. ACh (10-810-6 M) concentration-dependently increased endothelial [Ca2+]i and induced SMC hyperpolarization and relaxation. These SMC responses were blocked in the combined presence of apamin [blocker of small-conductance Ca2+-activated K+ (SKCa, KCa2.3) channel], TRAM 34 [blocker of intermediate-conductance Ca2+-activated K+ (IKCa, KCa3.1) channel] and margatoxin [blocker of subfamily of voltage-gated K+ (KV) channel, KV1]. CONCLUSIONS AND IMPLICATIONS In rabbit jugular vein, NO plays a primary role in endothelium-dependent relaxation at very low concentrations of ACh (10-1010-8 M). At higher concentrations, ACh (10-8-3 x 10-6 M) induces SMC hyperpolarization through activation of endothelial IKCa, KV1 and (possibly) SKCa channels and produces relaxation. These results imply that ACh regulates rabbit jugular vein tonus through activation of two endothelium-dependent regulatory mechanisms.
引用
收藏
页码:682 / 696
页数:15
相关论文
共 50 条
  • [32] Characteristics of hyperpolarization-activated inward current in rabbit pulmonary vein muscle sleeve cells
    LIU Jie
    HUANG Cong-xin
    JIANG Hong
    BAO Ming-wei
    CAO Feng and WANG Teng
    ChineseMedicalJournal, 2005, (23) : 2014 - 2019
  • [33] PKC isoforms involved in ACh-induced contraction of rat bronchial smooth muscle
    Kozutsumi, Yuri
    Yamamoto, Maki
    Sakai, Hiroyasu
    Chiba, Yoshihiko
    Misawa, Miwa
    ACTA PHARMACOLOGICA SINICA, 2006, 27 : 386 - 386
  • [34] ACH-INDUCED OSCILLATORY CURRENTS IN SWINE AIRWAY SMOOTH-MUSCLE CELLS
    LIU, XB
    FARLEY, JM
    FASEB JOURNAL, 1994, 8 (05): : A685 - A685
  • [35] Characteristics of hyperpolarization-activated inward current in rabbit pulmonary vein muscle sleeve cells
    Liu, J
    Huang, CX
    Jiang, H
    Bao, MW
    Cao, F
    Wang, T
    CHINESE MEDICAL JOURNAL, 2005, 118 (23) : 2014 - 2019
  • [36] ACh-induced endothelial NO synthase translocation, NO release and vasodilatation in the hamster microcirculation in vivo
    Figueroa, XF
    González, DR
    Martínez, AD
    Durán, WN
    Boric, MP
    JOURNAL OF PHYSIOLOGY-LONDON, 2002, 544 (03): : 883 - 896
  • [37] ATP- and ACh-induced responses in isolated cat petrosal ganglion neurons
    Alcayaga, Carmen
    Varas, Rodrigo
    Valdes, Viviana
    Cerpa, Veronica
    Arroyo, Jorge
    Iturriaga, Rodrigo
    Alcayaga, Julio
    BRAIN RESEARCH, 2007, 1131 (01) : 60 - 67
  • [38] Novel role for hydrogen peroxide in ach-induced dilation of human intestinal microvessels
    Hatoum, OA
    Binion, DD
    Miura, H
    Bosnjak, JJ
    Otterson, MF
    Telford, GL
    Gutterman, DD
    GASTROENTEROLOGY, 2004, 126 (04) : A254 - A254
  • [39] ACH-INDUCED LONG-LASTING ENHANCEMENT IN EXCITABILITY OF THE OLFACTORY-BULB
    ELAAGOUBY, A
    GERVAIS, R
    NEUROREPORT, 1992, 3 (01) : 10 - 12
  • [40] ROLE OF PROSTAGLANDIN PRODUCTION IN ACH-INDUCED CHLORIDE SECRETION IN RAT DISTAL COLON
    Yajima, Takaji
    Kaneko, Kenya
    Suzuki, Yuichi
    JOURNAL OF PHYSIOLOGICAL SCIENCES, 2009, 59 : 298 - 298