钙拮抗剂和Bay K 8644对兔耳动脉对外源性去甲肾上腺素和肾上腺素能神经刺激的收缩反应的不同影响。

Differential effects of calcium antagonists and Bay K 8644 on contractile responses to exogenous noradrenaline and adrenergic nerve stimulation in the rabbit ear artery.

作者信息

Skärby T V, Högestätt E D

机构信息

Department of Clinical Pharmacology, Lund University, Sweden.

出版信息

Br J Pharmacol. 1990 Dec;101(4):961-7. doi: 10.1111/j.1476-5381.1990.tb14188.x.

DOI:10.1111/j.1476-5381.1990.tb14188.x

PMID:1707708

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917846/

Abstract

The effects of three calcium antagonists (nifedipine, verapamil, diltiazem) and the calcium agonist Bay K 8644 were compared on contractile responses of similar amplitude elicited by noradrenaline (NA) and electrical nerve stimulation (ENS) in the rabbit isolated ear artery. 2. Contractions induced by both NA (3 x 10(-7) M) and ENS (10 Hz, 10s) were almost exclusively mediated by alpha 1-adrenoceptors, since 10(-7) M prazosin abolished (NA) or almost abolished (ENS) the responses, and prazosin was more than three orders of magnitude more potent than rauwolscine on both types of response. 3. ENS-induced contractions were considerably less inhibited by nifedipine, verapamil and diltiazem than were those elicited by NA. Bay K 8644 enhanced responses to NA more than those to ENS. 4. The inhibitory effect of nifedipine and Ca2+ deprivation on NA-induced contractions decreased with increasing NA concentration. Reduction of the NA response by prazosin or phenoxybenzamine increased the nifedipine inhibition. 5. Reduction of the ENS-induced contractions by prazosin or phenoxybenzamine, or by use of a lower stimulation frequency did not increase the inhibitory effect of nifedipine. 6. In conclusion, the differential effects of the calcium antagonists on NA- and ENS-induced contractions were not related to differences in alpha-adrenoceptor subtype (alpha 1/alpha 2), receptor reserve or response amplitude, but may rather reflect temporal and spatial differences in alpha-adrenoceptor activation between the responses.

摘要

比较了三种钙拮抗剂（硝苯地平、维拉帕米、地尔硫䓬）和钙激动剂Bay K 8644对家兔离体耳动脉中去甲肾上腺素（NA）和电刺激神经（ENS）引发的相似幅度收缩反应的影响。2. 由NA（3×10⁻⁷ M）和ENS（10 Hz，10 s）诱导的收缩几乎完全由α1 - 肾上腺素能受体介导，因为10⁻⁷ M哌唑嗪可消除（NA诱导的收缩）或几乎消除（ENS诱导的收缩）反应，并且哌唑嗪对这两种反应的效力比萝芙木碱强三个多数量级。3. 硝苯地平、维拉帕米和地尔硫䓬对ENS诱导的收缩的抑制作用比对NA诱导的收缩的抑制作用小得多。Bay K 8644增强对NA的反应比对ENS的反应更明显。4. 硝苯地平和Ca²⁺ 缺乏对NA诱导的收缩的抑制作用随NA浓度增加而降低。哌唑嗪或酚苄明降低NA反应会增加硝苯地平的抑制作用。5. 哌唑嗪或酚苄明降低ENS诱导的收缩，或使用较低的刺激频率，均不会增加硝苯地平的抑制作用。6. 总之，钙拮抗剂对NA和ENS诱导的收缩的不同作用与α - 肾上腺素能受体亚型（α1/α2）、受体储备或反应幅度的差异无关，而可能反映了两种反应之间α - 肾上腺素能受体激活的时间和空间差异。