SIÇAN İZOLE TORASİK AORTUNDA PERİVASKÜLER ADİPOZ DOKU FONKSİYONUNDAKİ YAŞA BAĞLI DEĞİŞİMİN IN VITRO VE IN VIVO ÇALIŞMALARLA DEĞERLENDİRİLMESİ

Abstract

Perivascular adipose tissue (PVAT) is the layer of fat surrounding the outside of blood vessels and contributes to the control of vascular tone through the release of relaxing factors that exhibit anticontractile effects under physiological conditions. In this thesis study, the anticontractile effect of PVAT was functionally characterized in the isolated thoracic aorta of rats. In the isolated thoracic aorta of young rats aged 10-12 weeks, contractions induced by norepinephrine (10-10 – 10-4 M) were reduced in the presence of PVAT, demonstrating the anticontractile effect of PVAT. The fact that these responses did not change in endothelium-denuded rings and in the presence of L-NAME (10-4 M) indicated that the anticontractile response of PVAT is endothelium-independent and mediated by a relaxing factor other than nitric oxide (NO). When examining the age-related changes in the anticontractile response of PVAT in 52-week-old adult rats, there was a slight but significant increase in norepinephrine-induced contraction sensitivity in tissues without PVAT. This increase was inhibited in the presence of PVAT, similar to young rats, indicating that the anticontractile function of PVAT persists in older rat and limits vascular contraction with its tonic inhibitory effect. However, when endothelium-dependent relaxations were examined, relaxations induced by acetylcholine (10-9 – 10-5 M) were reduced in both PVAT-removed and PVAT-intact tissues of older rats, unlike the young group. The protective role of PVAT on vascular reactivity was also examined in the presence of high fructose both in vitro and in vivo. The anticontractile function of PVAT persisted in arteries incubated with 40 mM fructose for 1 hour in the bath media and in isolated arteries from hypertensive rats induced by 10% fructose for 12 weeks. While acetylcholine-induced relaxations remained unchanged in the in vitro high fructose and mannitol groups, they significantly decreased in the presence of PVAT of the control group of fructose-induced rats, whereas they were prevented in the hypertensive group. According to these findings, the anticontractile effect of PVAT on contractions is maintained in older rats and in a fructose-related metabolic environment. However, it can be suggested that the regulatory role of PVAT on endothelial relaxations might be decreased with aging. Nevertheless, PVAT is potentiated possibly by altered adipocyte metabolism during the early stage of fructose-related metabolic disturbances, and different adipocyte-derived relaxing factors released by PVAT partially protect vascular function.