兔颈静脉乙酰胆碱诱导超极化和松弛的特征。

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

机构信息

Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Japan.

出版信息

Br J Pharmacol. 2012 Oct;167(3):682-96. doi: 10.1111/j.1476-5381.2012.02038.x.

DOI:10.1111/j.1476-5381.2012.02038.x

PMID:22595036

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3449270/

Abstract

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⁺) in endothelial cells but did not alter the SMC membrane potential. However, ACh (10⁻¹⁰ -10⁻⁸ M) induced a concentration-dependent relaxation during the contraction induced by PGF(2α) and this relaxation was blocked by the NO synthase inhibitor N(ω) -nitro-l-arginine. ACh (10⁻⁸ -10⁻⁶ M) concentration-dependently increased endothelial Ca²⁺ and induced SMC hyperpolarization and relaxation. These SMC responses were blocked in the combined presence of apamin [blocker of small-conductance Ca²⁺-activated K⁺ (SK(Ca) , K(Ca) 2.3) channel], TRAM 34 [blocker of intermediate-conductance Ca²⁺ -activated K⁺ (IK(Ca) , K(Ca) 3.1) channel] and margatoxin [blocker of subfamily of voltage-gated K⁺ (K(V) ) channel, K(V) 1].

CONCLUSIONS AND IMPLICATIONS

In rabbit jugular vein, NO plays a primary role in endothelium-dependent relaxation at very low concentrations of ACh (10⁻¹⁰ -10⁻⁸ M). At higher concentrations, ACh (10⁻⁸ -3 × 10⁻⁶ M) induces SMC hyperpolarization through activation of endothelial IK(Ca) , K(V) 1 and (possibly) SK(Ca) channels and produces relaxation. These results imply that ACh regulates rabbit jugular vein tonus through activation of two endothelium-dependent regulatory mechanisms.

摘要

背景与目的

在动脉中，已充分阐明了内皮细胞衍生的一氧化氮和前列环素以及内皮细胞超极化在乙酰胆碱（ACh）诱导的舒张中的作用。然而，静脉中 ACh 诱导舒张的机制仍有待充分阐明。

实验方法

在兔颈静脉完整内皮和去内皮的标本中测量了 ACh 诱导的平滑肌细胞（SMC）超极化和舒张。

主要结果

在完整内皮的标本中，ACh（≤10⁻⁸ M）仅轻微增加内皮细胞内钙离子浓度(Ca²⁺)，但不改变 SMC 膜电位。然而，ACh（10⁻¹⁰-10⁻⁸ M）在 PGF（2α）诱导的收缩期间诱导浓度依赖性舒张，这种舒张被一氧化氮合酶抑制剂 N（ω）-硝基-L-精氨酸所阻断。ACh（10⁻⁸-10⁻⁶ M）浓度依赖性地增加内皮Ca²⁺，并诱导 SMC 超极化和舒张。这些 SMC 反应在同时存在蜂毒素（小电导钙激活钾通道（SK(Ca)，K(Ca)2.3）的阻断剂）、TRAM 34（中间电导钙激活钾通道（IK(Ca)，K(Ca)3.1）的阻断剂）和玛格毒素（电压门控钾通道（K(V)）亚家族的阻断剂，K(V)1）的情况下被阻断。

结论与意义

在兔颈静脉中，NO 在非常低浓度的 ACh（10⁻¹⁰-10⁻⁸ M）下发挥内皮依赖性舒张的主要作用。在较高浓度时，ACh（10⁻⁸-3×10⁻⁶ M）通过激活内皮 IK(Ca)、K(V)1 和（可能）SK(Ca)通道诱导 SMC 超极化，并产生舒张。这些结果表明，ACh 通过激活两种内皮依赖性调节机制来调节兔颈静脉张力。