Keitoku M, Maruyama Y, Takishima T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Cardiovasc Res. 1990 Aug;24(8):614-22. doi: 10.1093/cvr/24.8.614.
The aim was to investigate the receptor mechanisms for different histamine actions in proximal and distal human coronary arteries.
Postmortem human coronary rings precontracted by 50 mM KCl were exposed to histamine (10(-8)-10(-4) M) in control and after treatment with 10(-5) M pyrilamine (an H1 receptor antagonist), or 10(-4) M cimetidine (an H2 receptor antagonist), and/or endothelial removal. Tension changes at the point of maximum relaxation (at 10(-5) M in most rings) were obtained.
Endothelium dependent relaxations to histamine were clearly distinguished from endothelium independent relaxations by their transient nature and their inhibition by pyrilamine, but not by cimetidine. While most distal rings (group I, n = 42/58) and only some of the proximal rings (group II, n = 10/83) showed greater than 50% relaxation with histamine, nearly half the proximal rings (group III, n = 40/83) showed only contraction. Significant differences were found between group I and III, but not II, in control [-66(SD 15.2)% v +25(20.4)%, p less than 0.001] and after pyrilamine treatment [-66(9.2)% v -25(12.0)%, p less than 0.001], cimetidine treatment [-30(25.5)% v +42(20.9)%, p less than 0.001] and endothelial removal [-24(37.1)% v +36(20.2)%, p less than 0.01]. However, a combination of cimetidine and endothelial removal resulted in a contraction to histamine which was similar among the three groups.
These results suggest that hypercontractility to histamine was found in proximal human coronary arteries, but not in distal ones, probably due to the reduction of both direct and endothelial mediated relaxations rather than to an increase in the contraction itself.
旨在研究人冠状动脉近端和远端不同组胺作用的受体机制。
将用50 mM氯化钾预收缩的尸检人冠状动脉环，在对照情况下以及在用10(-5) M 吡苄明（一种H1受体拮抗剂）或10(-4) M 西咪替丁（一种H2受体拮抗剂）治疗后和/或去除内皮后，暴露于组胺（10(-8)-10(-4) M）。记录在最大舒张点（大多数环中为10(-5) M）时的张力变化。
组胺引起的内皮依赖性舒张通过其短暂性以及被吡苄明而非西咪替丁抑制，与内皮非依赖性舒张明显区分开来。虽然大多数远端环（I组，n = 42/58）以及仅一些近端环（II组，n = 10/83）对组胺的舒张大于50%，但近一半的近端环（III组，n = 40/83）仅表现为收缩。在对照情况下[-66(标准差15.2)%对+25(20.4)%，p<0.001]、吡苄明治疗后[-66(9.2)%对-25(12.0)%，p<0.001]、西咪替丁治疗后[-30(25.5)%对+42(20.9)%，p<0.001]以及去除内皮后[-24(37.1)%对+36(20.2)%，p<0.01]，I组和III组之间存在显著差异，但I组和II组之间无显著差异。然而，西咪替丁和去除内皮的联合作用导致对组胺的收缩，这在三组中相似。
这些结果表明，人冠状动脉近端存在对组胺的高收缩性，而远端则不存在，这可能是由于直接和内皮介导的舒张减少，而非收缩本身增加所致。
