Phospholipase C-mediated vasorelaxing action of melatonin in rat isolated aorta

Kim, Shang-Jin; Baek, Sung-Soo; Kang, Hyung-Sub; Kim, Jin-Shang

Korean Journal of Veterinary Research 2005;45(4):507-515.

Shang-Jin Kim, Sung-Soo Baek, Hyung-Sub Kang, Jin-Shang Kim

Bio-Safety Research Institute, Chonbuk National University

흰쥐 대동맥에서 phospholipase C를 경유한 melatonin의 혈관 이완 작용

김상진, 백성수, 강형섭, 김진상

전북대학교 생체안전성연구소

Abstract

Melatonin, the principal hormone of the vertebral pineal gland, participates in the regulation of cardiovascular system in vitro and in vivo. However, the effects of melatonin on vascular tissues are still vague. The aim of this study was to assess the relationship between phospholipase C (PLC) and nitric oxide synthase (NOS)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling cascade in the relaxatory action of melatonin in isolated rat aorta. Melatonin induced a concentration-dependent relaxation in phenylephrine (PE)- and KCl-precontracted endothelium intact (+E) aortic rings. In KCl-precontracted +E aortic rings, the melatonin-induced vasorelaxation was not inhibited by endothelium removal or by pretreatment with NOS inhibitors, L-$N^G$-nitor-arginine (L-NNA) and L-$N^G$-nitor-arginine methyl ester (L-NAME), guanylate cyclase (GC) inhibitors, methylene blue (MB) and 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). In PE-precontracted +E aortic rings, the melatonin-induced vasorelaxation was inhibited by endothelium removal or by pretreatment with L-NNA, L-NAME, MB, ODQ and 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC). Moreover, in without endothelium (-E) aortic rings and in the presence of L-NNA, L-NAME, MB and ODQ in +E aortic rings, the melatonin-induced residual relaxations and residual contractile responses to PE were not affected by NCDC, a PLC inhibitor. It is concluded that melatonin can evoke vasorelaxation due to inhibition of PLC pathway through the protein kinase G activation of endothelial NOS/cGMP signaling cascade.

Key Words: aorta, cGMP, melatonin, NOS, 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate, vasorelaxation