Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries

The present study was designed to determine the effects of melatonin on cor onary vasomotor tone. Porcine coronary arteries were suspended in organ cha mbers for isometric tension recording. Melatonin (10(-10)-10(-5) M) itself caused neither contraction nor relaxation of the tissues. Serotonin (10(-9) -10(-5) M) caused concentration-dependent contractions of coronary arteries , and in the presence of melatonin (10(-7) M) the maximal response to serot onin was increased in rings with but not without endothelium. In contrast, melatonin had no effect on contractions produced by the thromboxane A(2) an alog U-46619 (10(-10) 10(-7) M). The melatonin-receptor antagonist S-20928 (10(-6) M) abolished the potentiating effect of melatonin on serotonin-indu ced contractions in endothelium-intact coronary arteries, as did treatment with 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin- 1-one (10(-5) M), methylene b lue (10(-5) M), or N-G-nitro- L-arginine (3 x 10(-5) M). In tissues contrac ted with U-46619, serotonin caused endothelium-dependent relaxations that w ere inhibited by melatonin (10(-7) M). Melatonin also inhibited coronary ar tery relaxation induced by sodium nitroprusside (10(-9)-10(-5) M) but not b y isoproterenol (10(-9)-10(-5) M). These results support the hypothesis tha t melatonin, by inhibiting the action of nitric oxide on coronary vascular smooth muscle, selectively potentiates the vasoconstrictor response to sero tonin in coronary arteries with endothelium.