Attenuation of Endothelium‐Related Relaxation and Enhanced Responsiveness of Vascular Smooth Muscle to Histamine in Spastic Coronary Arterial Segments From Miniature Pigs

Attenuation of Endothelium‐Related Relaxation and Enhanced Responsiveness of Vascular Smooth Muscle to Histamine in Spastic Coronary Arterial Segments From Miniature Pigs
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小型猪痉挛性冠状动脉节段内皮相关松弛的减弱和血管平滑肌对组胺反应性的增强

DOI:
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发表时间:
1987
影响因子:
20.1
通讯作者:
Motoomi Nakamura
Motoomi Nakamura
中科院分区:
医学1区
文献类型:
--
作者:
Y. Yamamoto;H. Tomoike;K. Egashira;Motoomi Nakamura

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冠状动脉痉挛的机制进行了研究,关于内皮相关的舒张和收缩产生的平滑肌细胞的痉挛血管分离哥廷根小型猪。在这些猪中,在内皮剥脱后3个月,在体内通过血管造影记录冠状动脉痉挛,并将冠状动脉痉挛和对照节段以其最佳长度悬挂在器官腔室中以产生张力。在痉挛冠状动脉和对照冠状动脉中,分别应用KCl(118 mM)、乙酰胆碱(10-9至10-4 M)和PGF 2 α(10-8至3 ± 10-5 M)产生相似的张力。在组胺(10 -8至3 ± 10-4 M; n= 14)和5-羟色胺(10-9至10-5 M; n= 13)浓度增加期间,痉挛血管的最大张力分别为118 mM KCl产生的张力的136 ± 6和97 ± 4%。这显著大于对照血管中观察到的:分别为98 ± 4和74 ± 4%。痉挛血管中组胺和5-羟色胺的ED 50也显著降低。机械去除内皮后,在累积给予组胺(n = 8)而不是5-羟色胺(n = 8)期间产生的张力在痉挛血管中比对照血管大,从而表明痉挛血管中平滑肌对组胺的反应增强。机械剥脱后最大张力的增加在对照组中大于组胺和5-羟色胺的痉挛血管。在PGF 2 α(10-5 M)预收缩条件下,检测了5-羟色胺(n = 5)和A23187(n = 5)引起的内皮依赖性舒张。5-羟色胺引起的最大舒张在痉挛血管和对照血管中分别为31 ± 4和67 ± 8%(p<0.01)。A23187完全松弛痉挛血管,与对照血管中观察到的程度相似;然而,在痉挛血管和对照血管中,A23187诱发的舒张ED 50分别为2.7 ± 0.6 ± 10-8和6.3 ± 1.4 ± 10-9 M(p<0.01)。因此,平滑肌对组胺的反应性增加和对5-羟色胺和组胺的内皮依赖性舒张功能受损可能在这些小型猪冠状动脉痉挛中观察到的过度收缩中起重要作用。
Mechanism of coronary spasm was examined regarding endothelium-related relaxation and contraction produced by smooth muscle cells of spastic vessels isolated from Göttingen miniature pigs. In these pigs, coronary artery spasm was documented angiographically in vivo three months after endothelial denudation, and spastic and control segments of the coronary artery were suspended in organ chambers at their optimal length for generating tension. Applications of KC1 (118 mM), acetylcholine(10-9 to 10-4 M), and PGF2α (10-8 to 3 ± 10-5 M) produced similar tension, at the respective doses, in both the spastic and control coronary arteries. During increasing concentrations of histamine (l0-8 to 3 ± 10-4 M; n= 14) and serotonin (10-9 to 10-5 M; n= 13), the maximum tension of the spastic vessel was 136 ± 6 and 97 ± 4%, respectively, of the tension produced by 118 mM KC1. That is significantly larger than seen in the control vessels: 98 ± 4 and 74 ± 4%, respectively. The ED50 to histamine and serotonin was also significantly less in the spastic vessels. After mechanical removal of the endothelium, the tension generated during the cumulative administration of histamine (n = 8) but not serotonin (n = 8) was larger in the spastic than the control vessels, thereby suggesting the presence of augmented responses of the smooth muscle to histamine in the spastic vessels. The increase in maximum tension after mechanical denudation was greater in the control than the spastic vessels in cases of histamine and serotonin. Endothelium-dependent relaxations due to serotonin (n = 5) and A23187 (n = 5) were tested under conditions of precontraction by PGF2α (10-5 M). The maximum relaxation induced by serotonin was 31 ± 4 and 67 ± 8% (p<0.01) in the spastic and the control vessel, respectively. A23187 relaxed completely the spastic vessel, to a similar extent as seen in the control vessels; however, the ED50 of relaxation evoked by A23187 was 2.7 ± 0.6 ± 10-8 and 6.3 ± 1.4 ± 10-9 M (p<0.01) in the spastic and the control vessels, respectively. Thus, both increased responsiveness of smooth muscle to histamine and impairment of endothelium-dependent relaxation to serotonin and to histamine may play an important role in the hypercontraction observed in coronary artery spasm in these miniature pigs.
DOI: 10.1172/jci112779
发表时间: 1987-01-01
影响因子: 15.9
作者:
BOSSALLER, C;HABIB, GB;HENRY, PD
通讯作者: HENRY, PD