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机构地区:[1]河北医科大学药学院药理研究室,石家庄050017 [2]华北制药康欣有限公司,石家庄050000
出 处:《中国药学杂志》2006年第10期754-758,共5页Chinese Pharmaceutical Journal
基 金:河北省自然科学基金(302481)
摘 要:目的建立兔离体隐动脉环双相血管收缩反应模型,利用哌唑嗪和α,β-亚甲基ATP(α,β-meATP)对双相收缩成分的特性进行药理学分析。方法兔离体隐动脉血管环张力记录法及电场刺激诱发血管收缩法。结果本实验条件下的电场刺激(电压15V、波宽1 ms、刺激频率2~16 Hz、连续刺激时程32 s)可诱发兔离体隐动脉产生双相收缩反应,且具有频率(2~16 Hz)依赖性。电刺激隐动脉收缩反应的第1相不被α_1受体阻断剂哌唑嗪(0.1~10μmol·L^(-1))所阻断,P2X_1受体激动剂α,β-meATP脱敏P2X_1受体后完全抑制该相反应。0.1~10μmol·L^(-1)哌唑嗪显著抑制8,16 Hz的第2相反应,P2X_1受体脱敏剂α,β-meATP不影响8,16 Hz的第2相反应。联合应用α,β-meATP(3μmol·L^(-1))和哌唑嗪(1μmol·L^(-1))则完全阻断电刺激诱发的血管收缩反应。哌唑嗪10μmol·L^(-1)显著抑制去甲肾上腺素(NA,0.01~30μmol·L^(-1))诱发的血管收缩反应,而哌唑嗪1μmol·L^(-1)对α,β- meATP诱发的血管收缩反应无显著性作用。α,β-meATP3μmol·L^(-1)对NA(0.01~30μmol·L^(-1))诱发的血管收缩反应无显著性影响。结论建立电场刺激诱发兔离体隐动脉环双相收缩反应模型,该双相反应的第一相仅与交感神经嘌呤能递质ATP的突触后效应有关,第2相反应由肾上腺素能成分和少量嘌呤能成分组成。OBJECTIVE To establish a biphasic vasoconstriction model induced by electrical stimulation, and analyze their characteristics of the biphasic vasoconstriction in the ring preparation of the rabbit saphenoas artery with the use of prazosin and α,β-meATP. METHODS Isometric vasoconstriction of the rabbit saphenous arterial rings was recorded, and the sympathetic nerves of the arterial rings were activated with electrical stimulation. RESULTS The biphasic neurogenic vasoconstriction was consistently induced by electrical stimulation ( 15 V, 1 ms pulse duration, 2 - 16 Hz for 32 s) in a frequency-related manner in the rabbit saphenous artery. The 1st phase of vasoconstriction induced by electrical stimulation was not blocked by prazosin (0.1 - 10μmol· L^- 1 ), an α1 adrenoceptor antagonist, but was completely inhibited by the treatment with α,β-meATP ( P2X1 receptor desensitization). The 2nd phase of vasoconstriction was significantly inhibited by prazosin (0.1 - 10 μmol·L^-1) at 8, 16 Hz and not influenced by α,β-meATP. Vasoconstriction induced by electrical stimulation was all inhibited with the treatment of a combination of prazosin ( 1 μmol· L^- 1 ) and α,β-meATP (3 μmol· L^- 1 ). Concentration-response curves for NA (0.01 - 30 μmol·L^-1) were markedly inhibited by prazosin( 10 μmol· L^-1), but 1 μmol· L^-1 prazosin didn't affected the vascular responses induced by α,β- meATP. Vasoconstrictive responds to exogenous NA ( 0.01 - 30 μmol· L^- 1 ) were not affected by 3 μmol·:^-1 α,β-meATP. CONCLUSION Biphasic vasoconstriction can be induced by electrical stimulation, The Ist phase of vasoconstrietion contains only a purinergic component, and the 2nd phase of vasoconstriction involves both adrenergic component and a small port of purinergic component.
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