The investigation of long term resveratrol treatment on endothelial reactivity and eNOS, iNOS expression on female and male rats

TEZ KONUSU: The investigation of long term resveratrol treatment on endothelialreactivity and eNOS, iNOS expression on female and male rats.ÖĞRENC N N ADI ve SOYADI: SELEN SÖYLEMEZTEZ DANIŞMANININ ADI ve SOYADI: FATMA AKARANAB L M DALI: FARMAKOLOJYILI:2007STATÜSÜ:DOKTORASUMMARYResveratrol, present in red wine, has powerful antioxidant, endothelialreactivity promoting and estrogen agonistic/antagonistic activity, but its interactionwith female hormone estrogen is unknown. Estrogens have endothelial reactivityincreasing, vasodilating and antioxidant properties. These effects explain the low-incidence of mortality from coronary heart disease in females before menopause. Aftermenopause, the risk of coronary heart disease in women almost equalize with in that ofmen.In this study, the effects of endothelium-dependent vasodilatory agentsacetylcholine, estrogen and HDL, on male and female rat aortae and the influence oflong term resveratrol treatment on vasodilator responses were investigated. The effect ofangiotensin II in aortic rings and the effect of resveratrol treatment to angiotensin IIresponses in both male and female were determined. The effect of resveratrol on eNOS,iNOS protein and eNOS mRNA expression in aortae were measured, plasma and aortanitrite level and plasma estrogen levels were investigated. Resveratrol level in plasmaand liver samples and aortae superoxide level were also measured. The amount ofresveratrol in liver homegenates was 40-50 ng/g. Plasma estrogen level was significantlydecreased in resveratrol treated groups.The results of this study suggest that, resveratrol treatment markedlyincreased endothelial relaxations to acetylcholine, estrogen and HDL, decreasedcontractions to angiotensin II and closed the gender differences observed both inendothelial relaxations and contractions.The increased endothelial reactivity inresveratrol treated animals could be related to increased nitric oxide and decreasedsuperoxide production. The results of this study could bring out importantcontributions to highlight the protective cardiovascular effects of resveratrol.