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

Abstract

The objective of this study was to understand the effect of acetylsalicylic acid (aspirin) on resistance arteries from mesentery and uterus. During pregnancy, the uterine vasculature undergoes consistent growth to provide sufficient uteroplacental blood flow, a process whose failure is associated with pregnancy complications characterized by high uterine vascular resistance. Uterine arcuate (UA) and mesenteric arteries (MA; diameter <300 µm) isolated from non-gravid, mid-gravid (day 14), and late-gravid rats (day 20) were exposed to aspirin (10-12 to 10-5 M). Further, in UA from late-gravid rats, aspirin was evaluated in presence of inhibitors of nitric oxide synthases, cyclooxygenase, cyclic nucleotides (cAMP, cGMP) and BK channels, and also on endothelium-denuded vessels. 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 that was reduced in vessels from late gravid animals at concentrations >10-7 M. Further, uterine vasodilation was significantly reduced when the endothelium was removed (p < 0.001), and by inhibitors of nitric oxide synthase (p < 0.001), cyclooxygenase synthase (p < 0.05), cyclic nucleotides cGMP/cAMP and BK channels. 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 - primarily endothelial - mechanisms. Our results in UA suggest that the use of aspirin may be effective in enhancing uteroplacental blood flow, while its vasodilation effect on MA may lower peripheral resistance.