Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors.
Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors.
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DOI：
10.1016/s0014-2999(01)01112-8
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发表时间：
2001-07
影响因子：
5
通讯作者：
J. Wagner;Zoltán Járai;S. Batkai;George Kunos
中科院分区：
文献类型：
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作者：
J. Wagner;Zoltán Járai;S. Batkai;George Kunos
外周大麻素 CB1 受体的激活会引起低血压。使用放射性微球技术，我们检查了大麻素对麻醉大鼠全身血流动力学的影响。有效的大麻素 CB1 受体激动剂 HU-210（{−}-11-OH-Δ9 四氢大麻酚二甲基庚基，10 μg/kg 静脉注射）通过将心脏指数从 37±1 降低至 23±2 ml/min/100 g，使平均血压降低 57±5 mm Hg (P<0.05)，但没有显着影响 全身血管阻力指数。神经节阻滞和加压素输注后，HU-210 引起类似的血压下降。内源性大麻素 anandamide（花生四烯基乙醇酰胺，静脉注射 4 mg/kg）通过将全身血管阻力指数从 3.3±0.1 降低至 2.3±0.1 mm Hg min/ml/100 g，使血压降低 40±7 mm Hg（P<0.05），而心脏指数和每搏输出量指数保持不变。 HU-210（anandamide）及其代谢稳定的类似物 R-methanandamide 可降低主要在冠状动脉和大脑中的血管阻力。当通过容量替代维持血压来防止自动调节时，这些血管舒张作用保持不变，但通过大麻素 CB1 受体拮抗剂 SR141716A 预处理可以防止 (N-{哌啶-1-基}-5-{4-氯苯基}-1-{2,4-二氯苯基}-4-甲基-1H-吡唑-3-甲酰胺HCl；3mg/kg静脉注射)。只有 anandamide 和 R-methanandamide 是肠系膜血管扩张剂。我们得出的结论是，大麻素通过直接激活血管大麻素 CB1 受体，而不是通过自身调节、交感神经张力降低或非大麻素代谢物的作用，在体内引起严重的冠状动脉和脑血管舒张。各种大麻素的血流动力学特征之间的差异可能反映了不同组织中大麻素CB1受体表达的定量差异和/或尚未识别的受体的参与。
Activation of peripheral cannabinoid CB1receptors elicits hypotension. Using the radioactive microsphere technique, we examined the effects of cannabinoids on systemic hemodynamics in anesthetized rats. The potent cannabinoid CB1receptor agonist HU-210 ({−}-11-OH-Δ9tetrahydrocannabinol dimethylheptyl, 10 μg/kg i.v.) reduced mean blood pressure by 57±5 mm Hg by decreasing cardiac index from 37±1 to 23±2 ml/min/100 g (P<0.05) without significantly affecting systemic vascular resistance index. HU-210 elicited a similar decrease in blood pressure following ganglionic blockade and vasopressin infusion. The endogenous cannabinoid anandamide (arachidonyl ethanolamide, 4 mg/kg i.v.) decreased blood pressure by 40±7 mm Hg by reducing systemic vascular resistance index from 3.3±0.1 to 2.3±0.1 mm Hg min/ml/100 g (P<0.05), leaving cardiac index and stroke volume index unchanged. HU-210, anandamide, and its metabolically stable analog, R-methanandamide, lowered vascular resistance primarily in the coronaries and the brain. These vasodilator effects remained unchanged when autoregulation was prevented by maintaining blood pressure through volume replacement, but were prevented by pretreatment with the cannabinoid CB1receptor antagonist SR141716A (N-{piperidin-1-yl}-5-{4-chlorophenyl}-1-{2,4-dichlorophenyl}-4-methyl-1H-pyrazole-3-carboxamide HCl; 3 mg/kg i.v.). Only anandamide and R-methanandamide were vasodilators in the mesentery. We conclude that cannabinoids elicit profound coronary and cerebral vasodilation in vivo by direct activation of vascular cannabinoid CB1receptors, rather than via autoregulation, a decrease in sympathetic tone or, in the case of anandamide, the action of a non-cannabinoid metabolite. Differences between the hemodynamic profile of various cannabinoids may reflect quantitative differences in cannabinoid CB1receptor expression in different tissues and/or the involvement of as-yet-unidentified receptors.