Jin Honghua, Koyama Toshihiro, Hatanaka Yukako, Akiyama Shinji, Takayama Fusako, Kawasaki Hiromu
Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Eur J Pharmacol. 2006 Jan 4;529(1-3):136-44. doi: 10.1016/j.ejphar.2005.10.060. Epub 2005 Dec 9.
The present study was designed to examine the vascular response to histamine in rat perfused mesenteric vascular beds with active tone. In preparations with intact endothelium, perfusion of histamine (1 nM-100 microM) produced a concentration-dependent vasodilation. Histamine-induced vasodilation was attenuated by L-NAME (nitric oxide (NO) synthase inhibitor, 100 microM) and olopatadine (histamine H(1) receptor antagonist, 1 microM) but not by lafutidine (histamine H(2) receptor antagonist, 1 microM). Cold-storage denervation (4 degrees C for 72 h) of the preparation with intact endothelium attenuated the histamine-induced vasodilation. In preparations without endothelium, histamine at low concentrations (1-100 nM) produced only a small and rapid vasodilation, whereas histamine at concentrations higher than 1 muM produced triphasic vascular responses: initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. Lafutidine abolished only the histamine-induced initial vasodilation. Olopatadine abolished the histamine-induced second vasoconstriction and third vasodilation. Cold-storage denervation of the denuded preparation abolished the histamine-induced second vasoconstriction and third vasodilation. These findings suggest that histamine induced endothelium-dependent vasodilation via endothelium histamine H(1) receptors and endothelium-independent vasodilation via smooth muscle histamine H(2) receptors. It is also suggested that the histamine-induced endothelium-independent vasoconstriction and vasodilation are mediated by histamine H(1) receptors and perivascular nerves.
本研究旨在检测具有主动张力的大鼠灌注肠系膜血管床对组胺的血管反应。在具有完整内皮的标本中，灌注组胺（1 nM - 100 μM）可产生浓度依赖性血管舒张。组胺诱导的血管舒张被L - NAME（一氧化氮合酶抑制剂，100 μM）和奥洛他定（组胺H(1)受体拮抗剂，1 μM）减弱，但不被拉呋替丁（组胺H(2)受体拮抗剂，1 μM）减弱。对具有完整内皮的标本进行冷储存去神经处理（4℃ 72小时）可减弱组胺诱导的血管舒张。在没有内皮的标本中，低浓度（1 - 100 nM）的组胺仅产生轻微且快速的血管舒张，而浓度高于1 μM的组胺则产生三相血管反应：最初的急剧血管舒张，随后是短暂的血管收缩，以及随后的逐渐血管舒张。拉呋替丁仅消除组胺诱导的初始血管舒张。奥洛他定消除组胺诱导的第二次血管收缩和第三次血管舒张。对去内皮标本进行冷储存去神经处理消除了组胺诱导的第二次血管收缩和第三次血管舒张。这些发现表明，组胺通过内皮组胺H(1)受体诱导内皮依赖性血管舒张，并通过平滑肌组胺H(2)受体诱导非内皮依赖性血管舒张。还表明，组胺诱导的非内皮依赖性血管收缩和血管舒张由组胺H(1)受体和血管周围神经介导。
