乙酰胆碱诱导的猴离体上、下腔静脉内皮依赖性舒张作用。

Acetylcholine-induced endothelium-independent relaxations in monkey isolated superior and inferior caval veins.

作者信息

Fukushima S, Ohhashi T

机构信息

1st Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.

出版信息

Br J Pharmacol. 1993 Aug;109(4):992-7. doi: 10.1111/j.1476-5381.1993.tb13719.x.

DOI:10.1111/j.1476-5381.1993.tb13719.x

PMID:8401953

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175750/

Abstract

We examined the effects of acetylcholine (ACh), isoprenaline (Isop) and Ca-ionophore, A23187 on monkey isolated superior (SCV) and inferior caval veins (ICV) with and without intact endothelium, which had been partially contracted by 2 x 10(-6)-5 x 10(-6) M prostaglandin F2 alpha (PGF2 alpha). 2. Low concentrations of ACh (10(-10)-10(-9) M) produced a dose-dependent relaxation in the precontracted venous segments with endothelium. ACh at concentrations more than 10(-7) M elicited a transient contraction followed by a relaxation in these segments. 3. An addition of 5 x 10(-7) M A 23187 induced about 60% of maximum relaxation produced by 10(-5) M sodium nitroprusside (SNP) in each venous segment with endothelium. 4. Isop (10(-10)-10(-5) M) caused a dose-related relaxation in the precontracted caval veins with intact endothelium. 5. Removal of endothelium caused no significant effect on the ACh-induced dual responses but a significant inhibition of the A23187-induced relaxation. 6. Pretreatment with atropine antagonized competitively the ACh-induced relaxations in the endothelium-intact and endothelium-denuded caval veins. The Schild plot analysis showed that the pA2 values of the segments with and without endothelium were 9.72 +/- 0.14 (n = 5) and 10.01 +/- 0.23 (n = 6) in the ICV; and 9.95 +/- 0.20 (n = 5) and 9.70 +/- 0.10 (n = 5) in the SCV, respectively. 7. Pretreatment with 5 x 10-5M aspirin, 3 x 10-5M N0-nitro-L-arginine methylester, 1 mM tetraethylammonium,or 3 x 10-6 M glibenclamide caused no significant effect on the basal tone, ACh induced transient contraction, and ACh;.induced relaxation in the precontracted venous segments with and without endothelium.8. Pretreatment with 10-5 M methylene blue produced a significant reduction of the ACh- and SNP induced relaxations in the precontracted venous segments with and without endothelium. The pretreatment with the same concentration of methylene blue, however, caused no significant effect on the Isop-induced relaxation in venous segments with endothelium.9. The results suggest that ACh acts directly on the venous smooth muscle cells via a high-affinity muscarinic receptor subtype to accumulate cellular cyclic GMP producing endothelium-independent relaxation in the monkey caval veins.

摘要

我们研究了乙酰胆碱（ACh）、异丙肾上腺素（Isop）和钙离子载体A23187对猴离体上腔静脉（SCV）和下腔静脉（ICV）的影响，这些静脉有或没有完整内皮，且已被2×10⁻⁶ - 5×10⁻⁶ M前列腺素F2α（PGF2α）部分收缩。2. 低浓度的ACh（10⁻¹⁰ - 10⁻⁹ M）使有内皮的预收缩静脉段产生剂量依赖性舒张。浓度超过10⁻⁷ M的ACh在这些段中引发短暂收缩，随后是舒张。3. 添加5×10⁻⁷ M A23187在每个有内皮的静脉段中诱导出约60%由10⁻⁵ M硝普钠（SNP）产生的最大舒张。4. Isop（10⁻¹⁰ - 10⁻⁵ M）使有完整内皮的预收缩腔静脉产生剂量相关的舒张。5. 去除内皮对ACh诱导的双重反应无显著影响，但对A23187诱导的舒张有显著抑制作用。6. 用阿托品预处理竞争性拮抗了有内皮和无内皮腔静脉中ACh诱导的舒张。Schild图分析表明，下腔静脉中有内皮和无内皮段的pA2值分别为9.72±0.14（n = 5）和10.01±0.23（n = 6）；上腔静脉中分别为9.95±0.20（n = 5）和9.70±0.10（n = 5）。7. 用5×10⁻⁵ M阿司匹林、3×10⁻⁵ M N⁰-硝基-L-精氨酸甲酯、1 mM四乙铵或3×10⁻⁶ M格列本脲预处理对有或无内皮的预收缩静脉段的基础张力、ACh诱导的短暂收缩和ACh诱导的舒张均无显著影响。8. 用10⁻⁵ M亚甲蓝预处理使有或无内皮的预收缩静脉段中ACh和SNP诱导的舒张显著降低。然而，用相同浓度的亚甲蓝预处理对有内皮的静脉段中Isop诱导的舒张无显著影响。9. 结果表明，ACh通过高亲和力毒蕈碱受体亚型直接作用于静脉平滑肌细胞，积累细胞内环鸟苷酸，在猴腔静脉中产生不依赖内皮的舒张。