Aspirin causes endothelium-dependent vasodilation of resistance arteries from non-gravid and gravid rats

Abstract

Objective:Theobjectiveofthisstudywastounderstandtheeffectofacetylsalicylicacid(aspirin)onresistancearteriesfrommesenteryanduterus.Duringpregnancy,the uterine vasculature undergoes consistent growth to provide sufficient uteroplacental blood flow, a process whose failure is associated with pregnancy compli-cations characterized by high uterine vascular resistance.Methods:Uterine arcuate (UA) and mesenteric arteries (MA; diameter<300μm) isolated from non-gravid, mid-gravid (day 14), and late-gravid rats (day 20) wereexposedtoaspirin(10−12to10−5M).Further,inUAfromlate-gravidrats,aspirinwasevaluatedinpresenceofinhibitorsofnitricoxidesynthases,cyclooxygenase,cyclic nucleotides (cAMP, cGMP) and BK channels, and also on endothelium-denuded vessels.Results:Aspirin dilated both UA and MA in a dose dependent manner. Pregnancy increased aspirin vasodilation in MA and UA from mid-gravid rats, an effect thatwas reduced in vessels from late gravid animals at concentrations>10−7M. Further, uterine vasodilation was significantly reduced when the endothelium wasremoved (p < 0.001), and by inhibitors of nitric oxide synthase (p < 0.001), cyclooxygenase synthase (p < 0.05), cyclic nucleotides cGMP/cAMP and BKchannels.Conclusion:This is the first study to show a direct vasodilatory effect of aspirin on rat uterine artery that is mediated by a combination of cellular – primarilyendothelial - mechanisms. Our results in UA suggest that the use of aspirin may be effective in enhancing uteroplacental blood flow,while its vasodilation effect onMA may lower peripheral resistance.