Botulinum toxin type A suppresses arterial vasoconstriction byregulating calcium sensitization and the endothelium-dependent endothelialnitric oxide synthase/soluble guanylyl cyclase/cyclic guanosine monophosphatepathway: An in vitro study

摘要

Botulinum toxin type A (BTX-A) is a potent neurotoxin that causes relaxation ofstriated muscle by inhibiting the release of acetylcholine at the neuromuscularjunction. Some studies have suggested that BTX-A treatment for Raynaud syndromeis safe and effective with few adverse reactions. However, the underlyingmechanism remains unclear. In the present study, we used both arterial ringsisolated from rabbits and human microvascular endothelial cells (HMEC-1) toevaluate the mechanism underlying the effects of BTX-A on arterialvasoconstriction induced by 5-hydroxytryptamine. The roles of calciumsensitization and the endothelial nitric oxide synthase (eNOS)/soluble guanylylcyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway were investigated.BTX-A caused a concentration-dependent decrease in the contraction ofendothelium-intact arteries and significantly reduced calcium sensitization inthe arteries. Inhibitors of eNOS (L-NAME) and sGC (methylene blue) bothsignificantly abolished the vasodilatory action of BTX-A. Furthermore, BTX-Aincreased eNOS activity and the cGMP level in dose- and time-dependent mannersand increased eNOS and sGC protein levels in a time-dependent manner in HMEC-1.Taken together, these findings indicate that BTX-A suppresses arterialvasoconstriction by regulating smooth muscle calcium sensitization and theeNOS/sGC/cGMP pathway.