Luteolin-induced vasorelaxation in uterine arteries from normal pregnant rats

Abstract

Background: The flavonoid, luteolin, promotes vasorelaxation in various arteries through endothelial-dependent and independent mechanisms. Although there is growing interest in the vasoactive effects of flavonoids on maternal vascular function during pregnancy, it is unknown whether luteolin elicits vasorelaxation in the uterine circulation. We tested the hypothesis that luteolin induces vasorelaxation via endothelial-dependent mechanisms in uterine arteries from normal pregnant rats during late gestation.

Methods: Uterine arteries and aortas were isolated from Sprague-Dawley rats at gestational day 19 and prepared for wire myography.

Results: The potency of luteolin-induced vasorelaxation was examined between uterine arteries and the aortas. By 50 µM of luteolin, there was complete relaxation (100.5 ± 5.2%) in uterine arteries as compared to aortas (27.5 ± 10.0%). Even the highest concentration of 100 µM luteolin produced less than half relaxation (43.6 ± 8.6%) in aortas compared to uterine arteries. We then explored if luteolin-induced vasorelaxation in uterine arteries from pregnant rats was mediated by endothelial-dependent vasorelaxation pathways, including nitric oxide synthase (NOS), cyclooxygenase (COX), or potassium (K⁺) channels. Blocking these pathways with N(G)-Nitro-l-arginine methyl ester hydrochloride (L-NAME), indomethacin, or tetraethylammonium (TEA)/high potassium chloride (KCl), respectively, did not alter luteolin responses in uterine arteries from pregnant rats. These findings suggested that endothelial factors may not mediate luteolin-induced vasorelaxation in uterine arteries during pregnancy. Indeed, experiments where the endothelium was removed did not alter luteolin-induced vasorelaxation in uterine arteries during pregnancy.

Conclusions: Luteolin directly promotes vasorelaxation in the medial smooth muscle layer of uterine arteries during normal pregnancy.

Keywords: Flavonoid; Pregnancy; Uterine artery; Vasculature; Women’s health.