Relationship between LTD4-induced endothelium-dependent vasomotor relaxation and cGMP

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.