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Diltiazem-induced vasodilatation of smooth muscle cells of the canine basilar artery.

Abstract：

:1 The effects of diltiazem on smooth muscle cells of the canine basilar artery were investigated by means of microelectrode, double sucrose gap and isometric tension recording methods. 2 The mean membrane potential of the smooth muscle cells was -49.8 mV and they were electrically quiescent. Diltiazem (over 10(-5) M) depolarized the membrane. After pretreatment with 5 and 10 mM tetraethylammonium (TEA), an outward current pulse (1 and 2 s in duration) produced a spike and this spike was abolished by application of 10(-5) M diltiazem. 3 The spike could also be generated by the excitatory junction potential (e.j.p.) evoked by perivascular nerve stimulation (0.05 ms in pulse duration) in the presence of 5 mM TEA. Diltiazem (greater than 10(-6) M) suppressed both the spike and the e.j.ps, the suppression being more apparent for spike generation. The amplitude of the e.j.ps was reduced by diltiazem in concentrations greater than 10(-6) M. The effects were dose-dependent: when the amplitude of e.j.ps was reduced by application of diltiazem, the resulting mechanical response was also proportionally smaller. 4 The contractions evoked by 128 mM [K]o, 10(-3) M adenosine 5'-triphosphate (ATP) or, NaCl-free solution were abolished in Ca-free solutions containing 2 mM EGTA, but the amplitude of caffeine-induced contraction (10 mM) was only slightly reduced. Diltiazem, in concentrations above 3 X 10(-7) M suppressed the contraction evoked by excess [K]o, ATP or caffeine, but the inhibitory action of diltiazem on the K-induced contraction was greatest. 5 Following pretreatment with 2.5 mM [Ca]o, a contraction was evoked by caffeine in Ca-free solution. The amplitude of the caffeine-induced contraction was increased by simultaneous application of 2.5 mM [Ca]o with 128 mM [K]o and to a lesser extent by simultaneous application of 2.5 mM [Ca]o with 5.9 mM [K]o. The amplitude of the caffeine-induced contraction generated in the presence of 5.9 mM or 128 mM [K]o was suppressed to the same extent by application of diltiazem [10(-5) M) during preincubation in [Ca]o. This result suggests that the Ca stored in cell is replenished by Ca-influx from [Ca]o during the resting and active states of the membrane, and that diltiazem has no effect on the mobilization of Ca stored in the cell. 6 Thus, diltiazem acts on the canine basilar artery suppressing the Ca-influx during the active condition as a Ca-spike suppressor and the voltage-dependent Ca-influx induced by excess [K]o or by chemical depolarization. Diltiazem has no effect on the Ca mobilization from the store site. This agent also suppresses the amplitude of e.j.ps due to inhibition of the release of chemical transmitter from nerve terminals following the suppression of the Ca-influx. Diltiazem appears to act as a vasodilator on the canine basilar artery.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Fujiwara S,Ito Y,Itoh T,Kuriyama H,Suzuki H

doi

10.1111/j.1476-5381.1982.tb09162.x

subject

Has Abstract

pub_date

1982-03-01 00:00:00

pages

455-67

issue

eissn

0007-1188

issn

1476-5381

journal_volume

pub_type

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Diltiazem-induced vasodilatation of smooth muscle cells of the canine basilar artery.