Secrest R J, Ohlstein E H, Chapnick B M
Department of Pharmacology, St. Louis University School of Medicine, Missouri.
J Pharmacol Exp Ther. 1988 Apr;245(1):47-52.
The objective of the present investigation was to determine whether cyclic GMP (cGMP) participated in endothelium-dependent leukotriene (LT) D4-induced relaxation of canine superior mesenteric artery. All experiments were performed with endothelium-intact arterial rings, and tone was measured with isometric force displacement transducers. After tone had been induced with norepinephrine, LTD4 acetylcholine (ACh), nitroglycerin (GTN) and isoproterenol (ISOP), each produced concentration-dependent vasomotor relaxation. Because contractile responses produced by norepinephrine were enhanced in presence of methylene blue, the concentration of norepinephrine was reduced in order to induce tone that was equivalent to control. After this adjustment, incubation of the rings with methylene blue attenuated relaxation produced by LTD4, ACh and GTN, whereas ISOP-induced decreases in tone were unaltered. In addition, results of a separate series of experiments showed that cGMP levels in the arterial rings were enhanced at the time of peak relaxation produced in response to LTD4, ACh and GTN. In contrast to these observations, ISOP-induced relaxation was not associated with a change in cGMP concentration. When taken together, these results suggest that cGMP serves as a participant in endothelium-dependent relaxation produced by both LTD4 and ACh, as well as endothelium-independent relaxation produced by GTN.
本研究的目的是确定环磷酸鸟苷（cGMP）是否参与内皮依赖性白三烯（LT）D4诱导的犬肠系膜上动脉舒张。所有实验均使用内皮完整的动脉环进行，并使用等长力位移换能器测量张力。在用去甲肾上腺素、白三烯D4、乙酰胆碱（ACh）、硝酸甘油（GTN）和异丙肾上腺素（ISOP）诱导张力后，每种药物均产生浓度依赖性的血管舒张。由于在亚甲蓝存在下，去甲肾上腺素产生的收缩反应增强，因此降低去甲肾上腺素的浓度以诱导与对照相当的张力。经过这种调整后，将动脉环与亚甲蓝一起孵育会减弱白三烯D4、ACh和GTN产生的舒张作用，而异丙肾上腺素诱导的张力降低则未改变。此外，另一系列实验的结果表明，在对白三烯D4、ACh和GTN产生的最大舒张反应时，动脉环中的cGMP水平升高。与这些观察结果相反，异丙肾上腺素诱导的舒张与cGMP浓度的变化无关。综合来看，这些结果表明，cGMP参与了白三烯D4和ACh产生的内皮依赖性舒张以及硝酸甘油产生的非内皮依赖性舒张。
