2-烟酰胺基乙基硝酸盐对兔主动脉中激动剂敏感性Ca++释放和Ca++内流的影响。

Effects of 2-nicotinamidoethyl nitrate on agonist-sensitive Ca++ release and Ca++ entry in rabbit aorta.

作者信息

Hester R K

出版信息

J Pharmacol Exp Ther. 1985 Apr;233(1):100-11.

Abstract

The effects of 2-nicotinamidoethyl nitrate (SG-75) on norepinephrine (NE)- and KCI-induced responses in rabbit aorta were quantitated, correlated with 45Ca studies and compared with the effects of nifedipine (NIF) on similar parameters. NE- and KCI-induced dose-response relationships were differentially depressed by SG-75 (NE much greater than KCI) and NIF (KCI much greater than NE). Responses to KCI were relatively insensitive to prior SG-75, yet moderately relaxed by subsequent SG-75. Conversely, NIF markedly inhibited and completely relaxed similar responses. Responses to NE were relaxed and inhibited with SG-75, but unaffected by NIF. Responses to NE in La or O-Ca++ + ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid plus D600 (with and without KCI) solutions were phasic, reduced by SG-75 and insensitive to NIF. NE-dependent, Ca++-induced responses in a O-Ca++ + ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid plus D600 solution (with and without KCI) were attenuated by SG-75. Equilibrated (60 min) La -resistant (residual), high apparent affinity Ca++ binding was increased 26% with SG-75 and decreased 34% with NIF, yet neither altered the rate of exchange (10 min). Rate of exchange at low apparent affinity, residual sites was increased 21% by SG-75 without altering equilibrated values, whereas NIF reduced equilibrated values 11%, without affecting rate. NE reduced, SG-75 + NE augmented and NIF + NE decreased, in an additive fashion, high apparent affinity, residual bound Ca++. Residual Ca++ binding at low apparent affinity sites was increased with 160 mM substituted KCI (380%). This increase was only partially inhibited with SG-75, and eliminated by NIF. Net Ca++ efflux was persistently slowed by SG-75 and unaltered by NIF. The primary effects of SG-75 appear to be depression of Ca++ release and inhibition of receptor-operated (potential-independent) Ca++ entry, with limited attenuation of voltage-dependent Ca++ entry. NIF primarily inhibits voltage-dependent Ca++ entry.

摘要

对2-烟酰胺基硝酸乙酯（SG-75）对兔主动脉中去甲肾上腺素（NE）和氯化钾（KCI）诱导反应的影响进行了定量分析，与45Ca研究结果相关联，并与硝苯地平（NIF）对类似参数的影响进行了比较。SG-75（NE的影响远大于KCI）和NIF（KCI的影响远大于NE）对NE和KCI诱导的剂量反应关系有不同程度的抑制作用。对KCI的反应对预先使用的SG-75相对不敏感，但随后使用SG-75可使其适度舒张。相反，NIF能显著抑制并完全舒张类似反应。对NE的反应经SG-75处理后舒张并受到抑制，但不受NIF影响。在镧（La）或零钙（O-Ca++）+乙二醇双（β-氨基乙基醚）N，N'-四乙酸加D600（有或无KCI）溶液中对NE的反应呈阶段性，经SG-75处理后降低，对NIF不敏感。在O-Ca++ +乙二醇双（β-氨基乙基醚）N，N'-四乙酸加D600溶液（有或无KCI）中，NE依赖性、钙离子（Ca++）诱导的反应经SG-75处理后减弱。经60分钟平衡的耐镧（残留）、高表观亲和力的Ca++结合量，SG-75使其增加26%，NIF使其减少34%，但两者均未改变交换速率（10分钟）。SG-75使低表观亲和力残留位点的交换速率增加21%，而不改变平衡值，而NIF使平衡值降低11%，但不影响速率。NE使高表观亲和力、残留结合的Ca++减少，SG-75加NE使其增加，NIF加NE使其减少，呈相加作用。在160 mM取代氯化钾（380%）存在时，低表观亲和力位点的残留Ca++结合量增加。这种增加仅部分被SG-75抑制，而被NIF消除。SG-75持续减慢净Ca++外流，NIF对其无影响。SG-75的主要作用似乎是抑制Ca++释放和抑制受体操纵的（电位无关的）Ca++内流，对电压依赖性Ca++内流的减弱作用有限。NIF主要抑制电压依赖性Ca++内流。