The functional effects of visfatin in isolated rat mesenteric small resistance arteries

Adipose tissue is an endocrine organ with many vital roles as well as energy storage. In addition to the release of fatty acids, other lipids and metabolites, it secretes more than 600 bioactive factors named as adipokine (adipocytokine). Adipocytokines can exert both local effects within the adipose tissue and systemic effects in different organs by reaching them through systemic. More than 600 adipokines, currently known, play roles in biological processes such as immune response, inflammation, glucose metabolism, insulin sensitivity, hypertension, cell adhesion, vascular growth and function, adipogenesis, bone morphogenesis, growth, lipid metabolism and regulation of appetite and satiety. Visfatin, a new adipocytokine, is expressed in perivascular adipose tissue (PVAT) and exerts effects in vascular system in addition to its relation with various pathological conditions. It is suggested that visfatin is a potential biomarker for endothelial dysfunction and vascular damage. Although, it is reported that visfatin may play a direct role in deterioration of vascular relaxation, there are conflicting results regarding its functional effects in small resistance arteries. Therefore, the present study aimed to investigate the functional effects and the possible underlying mechanism(s) of visfatin in isolated rat mesenteric small resistance arteries. The study was conducted in isolated rings of small resistance arteries from mesenteric vascular bed obtained from male Wistar rats aged 10-12 weeks. While visfatin incubation (1, 5, 25, 50 and 100 ng/mL) did not produce significant alterations in contractile responses of mesenteric arterial rings to noradrenaline (NA: 10-10 – 10-5 M), relaxation responses to acetylcholine (ACh: 10-10 – 10-5 M) were significantly reduced in endothelium-intact rings. The inhibitory effect of visfatin was not observed in endothelium-denuded rings. Incubation of tissues with Nampt inhibitor FK866 (10 µM) or superoxide dismutase (SOD: 100 U/ml) reversed the inhibitory effects of visfatin on relaxation responses to ACh. Visfatin incubation did not cause a significant alteration in relaxation responses of rat mesenteric artery rings to sodium nitroprusside (SNP: 10-10 – 10-5 M). Mesenteric PVAT visfatin levels (117.75 ± 12.47 ng/mg) were significantly higher than plasma visfatin levels (8.75 ± 0.81 ng/mL) and there was a significant positive correlation between these two parameters. Taken together, present results suggested that visfatin inhibited the endothelium-dependent relaxation responses in isolated rat mesenteric resistance arteries probably through NO inhibition and free oxgen radicals. Given that NO is a vasoprotective agent inhibiting endothelial inflammation and thrombosis, the results of our study indicated that increments in local and/or systemic visfatin levels due to various pathological conditions may contribute, at least at the level of small resistance arteries through unfavorable effects on endothelial functions, in these pathologies. Keywords:Adipokine, Visfatin, Rat Mesenteric Artery, Nitric Oxide, Vasoprotective