Melatonin inhibits NO‐induced cGMP accumulation in porcine coronary arteries

Abstract

Recent studies in our laboratory indicate that melatonin modulates vascular tone by interfering with nitric oxide (NO) signaling in coronary arteries. Here we tested the hypothesis that melatonin impairs NO‐induced vasorelaxation by inhibiting the NO‐induced increase in cGMP levels in coronary arteries. In organ bath studies, sodium nitroprusside (SNP) (10−9‐10−5 M) caused relaxation of isolated porcine coronary artery rings. Incubation of the tissues with melatonin (10−7 M) caused a rightward shift in the SNP concentration‐response curve. In the presence of the phosphodiesterase inhibitor, zaprinast (10−5 M), the inhibitory effect of melatonin on SNP‐induced vasorelaxation was abolished. Melatonin (10−7 M) had no effect on basal cGMP levels but markedly inhibited the SNP‐induced increase in cGMP. The effect of melatonin on cGMP accumulation was significantly diminished by incubation of the tissues with either zaprinast (10−5 M) or the MT2‐receptor antagonist, 4P‐PDOT (10−7 M). The expression of MT2‐receptors in coronary arteries was confirmed by immunoblot analysis. Taken together, these results suggest that the inhibitory effect of melatonin on NO signaling in coronary arteries is most likely due to impaired cGMP accumulation in response to NO. The inhibitory effect of melatonin is mediated by MT2‐receptors, perhaps via a mechanism that is coupled to increased phosphodiesterase activity.