혈관 평활근 수축에 미치는 melatonin의 효과

Effects of melatonin on contraction in rat aortic smooth muscle

Vasodilatory effects of melatonin, the pineal hormone, were examined on the isolated rat aorta. Melatonin caused a sustained relaxation of rat aorta contracted with norepinephrine (NE), endothelin-1 (ET-1) and high KCI. The agonist-induced contraction was partially attenuated by verapamil, a voltage dependent Ca²⁺ channel blocker. Additional treatment of melatonin abolished the agonist-induced verapamil-resistant contraction, completely. Melatonin also inhibited 12-deoxyphorbol 13-isobutyrate (DPB, 1μM)-induced contraction in Ca²⁺-free physiological salt solution (PSS). These results show that melatonin effects on the contractile protein contributes to contraction in aortic smooth muscle. To investigate the mechanism of relaxation of melatonin, inhibitors of cyclooxygenase, nitric oxide synthase and guanylate cyclase were applied to the aorta relaxed by melatonin. Neither indomethacin (10μM), a cyclooxygenase inhibitor, nor NG-nitro-L-arginine (L-NNA, 10μM), a nitric oxide synthase inhibitor, altered the melatonin-induced relaxation. The melatonin-induced relaxation was abolished by the pretreatment of 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), a selective guanylate cyclase inhibitor, but not by methylene blue, a non-selective guanylate cyclase inhibitor. In conclusion, melatonin induces relaxation of rat aorta by activation of guanylate cyclase, which inhibits contractile protein(s) in aortic smooth muscle.