Gender-specific effects of luteolin in the enhancement of endothelium-dependent relaxation in 45-50 weeks old rat mesenteric arteries: role of endothelium-derived hyperpolarizing factors and cyclooxygenase

Abstract

OBJECTIVE Luteolin is a non-steroidal polyphenols 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 organ chambers filled with Kreb's solution and bubbled with 95%O_2 and 5%CO_2.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) mol•L~(-1)) 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) mol•L~(-1),COX inhibitor) and L-NAME(10~(-5) mol•L~(-1),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 (IK_(Ca)) and small calcium-activated potassium channel(SK_(Ca)).However, in the presence of L-NAME, UCL 1684 (10~(-6) mol•L~(-1), SK_(Ca) blocker) and TRAM-34 (10~(-6) mol•L~(-1), IK_(Ca) blocker), luteolin produced a smaller enhancement of COX-mediated relaxation in male than that in female. CONCLUSION 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.