Vasodilator and hypotensive effects of the spider peptide Lycosin-I in vitro and in vivo

摘要

Highlights ? Lycosin-I induces a dose-dependent relaxation in endothelium-intact aortic rings. ? L-NAME (NOS inhibitor) and ODQ (sCG inhibitor) inhibit the vasodilator effects induced by Lycosin-I. ? NO, produced by eNOS, is induced by Lycosin-I. ? Lycosin-I has transient hypotension effect in vivo. Abstract Lycosin-I, a spider peptide isolated from the venom of the spider Lycosa singoriensis , has anti-bacteria and anti-cancer properties in organisms. However, cardiovascular effects of Lycosin-I have not been studied. In this study, we investigated for the first time the vasodilator and hypotensive effects of Lycosin-I and the possible mechanisms, in order to develop a promising treatment for hypertension-related diseases. For in vitro experiments, thoracic aortas were isolated, and divided into two groups, endothelium-intact and endothelium-denuded aortic rings. Lycosin-I induced a remarkable dose-dependent relaxation in endothelium-intact aortic rings pre-treated with phenylephrine ( p ? p ?>?0.05). The vasodilator effects of Lycosin-I were significantly weakened by a nitric oxide synthase (NOS) inhibitor, L-NAME ( p? ?0.001) and a selective inhibitor of nitric oxide (NO)-sensitive soluble guanylate cyclase (sGC), ODQ ( p? ?0.05), respectively. The levels of endothelial nitric oxide synthase (eNOS) phosphorylation and the NO production were significantly higher in human umbilical vascular endothelial cells pre-cultured with Lycosin-I than the control ( p? ?0.001), determined via western blot analysis and ozone-chemiluminescence technology. For in vivo experiments, arterial and venous catheters were inserted for mean arterial pressure (MAP) recording and drug administration in anaesthetized spontaneously hypertensive rats. Lycosin-I caused a transient drop of MAP 2?min after the administration compared with the control ( p? ?0.001). In conclusion, Lycosin-I has the potential to be an anti-hypertensive drug by endothelium-dependent vasodilatation, in which eNOS and NO-sensitive sGC are two main involved factors.