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The present study aimed to investigate the cellular mechanism of melatonin in aortic and tracheal smooth muscle tone via cytochrome p 450 and cyclooxygenase (COX) pathways.  Two experiments were carried out. In the first experiment, the aorta pre-incubated with melatonin, cyclooxygenase and epoxygenase inhibitors then contracted with PE, and dose response curve made to SNP and sildenafil as the following groups:  Group 1: Controls, after reaching the initial tension, the aorta contracted with phenylephrine (PE) and when reaches the plateau the concentrations of SNP, sildenafil added dose by dose to reach the maximal relax of aorta. Group 2: Melatonin, the aorta pre-incubated for 20 minutes with melatonin then contracted with PE. Group 3: COX inhibitor, the aorta incubated with indomethacin , then contracted by PE and relaxed by SNP, and Sildenafil doses.  Group 4: Cytochrome P450 inhibitor ,the aorta pre-incubated for 20 minutes with clotrimazole then contracted by PE and relaxed by SNP, and Sildenafil doses. In the second experiment, the trachea pre-incubated with melatonin , cyclooxygenase and epoxygenase inhibitors then contracted with acetylcholine (ACh)  and dose response curve made to SNP and Sildenafil and the same  groups were run as the first experiment. Data analysis revealed that indomethacin pre-incubation shifted the DRC of Sildenafil to the left significantly and it did not cause a significant change in Emax and p IC50. The present results of clotrimazole and clotrimazole with melatonin indicated that there was no significant change in Emax.  p IC50 slightly changed  causing the curve of clotrimazole to shift to the right slightly.  Tracheal rings that are pre-incubated with clotrimazole  tended to increase pIC50, while it reduced Emax .  Interestingly, the DRC  shifted to the right by melatonin pre-incubation. Furthermore, clotrimazole as compared with clotrimazole and melatonin pre-incubation shifted the DRC to the right. In conclusions, the present finding suggested that the relaxant effects of melatonin may partially returned to inhibiting COX and cytochrome p450 pathways in both trachea and aortic tissues.

Mechanism of the relaxant effects of melatonin via cyclooxygenase and epoxygenase pathways in male rat isolated aorta and trachea