Effect of luteolin on endothelium-dependent relaxation is different between male and female rat mesenteric arteries: relationship with endothelium-derived hyperpolarizing factor and cyclooxygenase pathways

Abstract

BACKGROUND: Luteolin is a non-steroidal polyphenolic plant metabolite which has similar structure with estrogen. The present study focused on whether or not luteolin produced gender-specific effects on relaxations that were mediated by different endothelium-derived factors. METHODS: Mesenteric arteries were isolated from 45-50 weeks old male and female Sprague Dawley rats, and incubated in the organ chambers filled with Kreb’s solution and bubbled with 95% O2 and 5% CO2. Endothelium-dependent relaxations mediated by nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF) and cyclooxygenase (COX) products were studied. RESULTS: Our data showed that luteolin (10-5 M) enhanced endothelium-dependent relaxation in general and NO-mediated relaxations in both male and female rat mesenteric arteries, and the degree of these enhancements did not differ between the two genders. In the presence of indomethacin (10-6 M, COX inhibitor) and L-NAME (10-5 M, NO synthase inhibitor), EDHF-mediated relaxation were enhanced by luteolin in a greater manner in male than that in female. This phenomenon was also observed in relaxation mediated by intermediate conductance calcium-activated potassium channel (IKCa) and small calcium-activated potassium channel (SKCa). However, in the presence of L-NAME, UCL 1684 (10-6 M, SKCa antagonist) and TRAM-34 (10-6 M, IKCa antagonist), luteolin produced a smaller enhancement of COX-mediated relaxation in male than that in female. CONCLUSIONS: In conclusion, luteolin selectively enhanced EHDF signaling pathways and this enhancement was greater in male than in female. On the other hand, luteolin caused greater activation of COX pathway in female than in male. Further study will focus on the expression of COX and potassium channels in both male and female rats.