Miller W L, Bove A A
Cardiovascular Division, Mayo Clinic, Rochester, Minnesota 55905.
Circ Res. 1988 Feb;62(2):226-32. doi: 10.1161/01.res.62.2.226.
The contributions of histamine (H1 or H2) receptor-mediated responses and, therefore, the effects of histamine blocking agents are unclear with regard to regulation of proximal epicardial and distal resistance coronary arteries. This study was designed to evaluate the effects of selective H1- and H2-receptor antagonists on epicardial and resistance vessels in the closed chest dog model. Histamine, diphenhydramine (H1 blocker), and cimetidine (H2 blocker) were infused into the left anterior descending coronary artery (LAD), and responses were studied by quantitative coronary angiography and flow measurements (133Xe washout). Histamine infusion alone produced a significant dilation of the proximal LAD (13% above control) only at the highest dose (45 micrograms/min), while LAD flow was increased by 128%. In the presence of H1 blocker, histamine produced significantly greater epicardial dilation (55% above control). The flow response curve was shifted to the right in the presence of H1 blocker, but the flow attenuation was overcome by the highest histamine dose. In contrast, the H2 blocker attenuated both epicardial dilation (6% below control) and flow response (31% above control) to the highest histamine dose. Results support a differential regulation of proximal epicardial and distal resistance vessels to histamine with epicardial arteries demonstrating H1-mediated vasoconstriction and H2-mediated vasodilation and distal resistance vessels showing H1- and H2-mediated vasodilation. In addition, these findings suggest that H1 blockade may antagonize histamine-related vasoconstriction and vasospasm, while H2 blockers may permit unopposed H1-mediated vasoconstriction of epicardial arteries and also limit resistance vessel vasodilatory responsiveness in the presence of elevated tissue histamine, as may occur in atherosclerotic coronary artery disease.
关于组胺（H1或H2）受体介导的反应以及组胺阻断剂的作用，在近端心外膜和远端阻力冠状动脉的调节方面尚不清楚。本研究旨在评估选择性H1和H2受体拮抗剂对闭胸犬模型中心外膜血管和阻力血管的影响。将组胺、苯海拉明（H1阻断剂）和西咪替丁（H2阻断剂）注入左冠状动脉前降支（LAD），并通过定量冠状动脉造影和血流测量（133Xe洗脱）研究其反应。单独输注组胺仅在最高剂量（45微克/分钟）时使近端LAD显著扩张（比对照高13%），而LAD血流量增加了128%。在存在H1阻断剂的情况下，组胺产生了显著更大的心外膜扩张（比对照高55%）。在存在H1阻断剂的情况下，血流反应曲线向右移动，但最高剂量的组胺克服了血流衰减。相比之下，H2阻断剂减弱了对最高组胺剂量的心外膜扩张（比对照低6%）和血流反应（比对照高31%）。结果支持近端心外膜血管和远端阻力血管对组胺的调节存在差异，心外膜动脉表现为H1介导的血管收缩和H2介导的血管舒张，而远端阻力血管表现为H1和H2介导的血管舒张。此外，这些发现表明，H1阻断可能拮抗组胺相关的血管收缩和血管痉挛，而H2阻断剂可能允许心外膜动脉不受抑制的H1介导的血管收缩，并且在组织组胺升高的情况下（如在动脉粥样硬化性冠状动脉疾病中可能发生的情况）也限制阻力血管的血管舒张反应性。
