Pan M, Scriabine A, Steinsland O S
Miles Institute for Preclinical Pharmacology, New Haven, Connecticut.
J Cardiovasc Pharmacol. 1988 Feb;11(2):127-33.
BAY K 8644 at 6.25 nM to 1 microM enhanced, in a concentration-dependent manner, both phases of the vasoconstrictor response of the isolated perfused rabbit ear artery to electrical stimulation. At 1 microM, BAY K 8644 enhanced the constrictor response by more than 250%. To study possible involvement of neurotransmitter release in the enhancement of the vasoconstrictor response by BAY K 8644, rabbit ear arteries were preincubated with [3H]norepinephrine and stimulated either electrically (for 1 or 5 min) or by 60 mM K+. BAY K 8644 (1 microM) had no effect on tritium release caused by 1-min periods of electrical stimulation. However, tritium release caused by 5-min periods of electrical stimulation or by 60 mM K+ was enhanced in the presence of BAY K 8644. It was concluded that BAY K 8644 enhances vasoconstrictor effects of electrical stimulation of rabbit ear artery by primarily a direct agonist action on Ca2+ channels in vascular smooth muscle cells. Following sustained depolarization, however, the drug may also enhance the release of neurotransmitter from sympathetic nerve endings. Under certain conditions, this release may contribute to the overall action of BAY K 8644.
BAY K 8644在6.25 nM至1 μM浓度范围内，以浓度依赖的方式增强了离体灌注兔耳动脉对电刺激的血管收缩反应的两个阶段。在1 μM时，BAY K 8644使收缩反应增强了250%以上。为了研究神经递质释放可能参与BAY K 8644增强血管收缩反应的过程，将兔耳动脉预先用[3H]去甲肾上腺素孵育，然后用电刺激（1或5分钟）或用60 mM K+刺激。BAY K 8644（1 μM）对1分钟电刺激引起的氚释放没有影响。然而，在BAY K 8644存在的情况下，5分钟电刺激或60 mM K+引起的氚释放增加。得出的结论是，BAY K 8644主要通过对血管平滑肌细胞中Ca2+通道的直接激动剂作用来增强兔耳动脉电刺激的血管收缩作用。然而，在持续去极化后，该药物也可能增强交感神经末梢神经递质的释放。在某些情况下，这种释放可能有助于BAY K 8644的整体作用。
