Akdeniz University, Medical Faculty, Department of Medical Pharmacology, Antalya, Turkey.
Akdeniz University, Medical Faculty, Department of Medical Pharmacology, Antalya, Turkey.
Eur J Pharmacol. 2021 Oct 5;908:174333. doi: 10.1016/j.ejphar.2021.174333. Epub 2021 Jul 17.
A new adipocytokine, visfatin is expressed in perivascular adipose tissue (PVAT) and exerts effects on vascular system in addition to its relationship with various pathological conditions. The present study aimed to investigate the functional effects of visfatin and the possible underlying mechanism(s) of the effects of visfatin in isolated rat mesenteric small resistance arteries. The study was conducted in small resistance arterial rings isolated from rat mesenteric vascular beds. While visfatin incubation did not produce significant alterations in contractile responses of mesenteric arterial rings to noradrenaline, relaxation responses to acetylcholine but not to sodium nitroprusside (SNP) were significantly reduced in endothelium-intact rings. The inhibitory effect of visfatin on responses to acetylcholine was not observed in endothelium-denuded preparations. Incubation of tissues with nicotinamide phosphoribosyl transferase (NAMPT) inhibitor FK866 or superoxide dismutase (SOD) reversed the inhibitory effects of visfatin on relaxation responses to acetylcholine. Co-incubation of visfatin with Nω-nitro-L-arginine methylester (L-NAME) did not produce a significant alteration in vascular responses to acetylcholine compared to L-NAME incubation alone. Mesenteric PVAT visfatin levels were significantly higher than and correlated positively with plasma visfatin levels. The results of our study indicated that visfatin-induced reductions in endothelium-dependent relaxations of rat isolated small resistance arteries are mediated by oxygen free radicals and a reduction in nitric oxide (NO) bioavailability. It was suggested that increment in systemic and/or local visfatin levels due to various pathologies including obesity and excessive weight gain may play a substantial role in initiation and/or propagation of vascular dysfunctions.
一种新的脂肪细胞因子内脂素在血管周围脂肪组织（PVAT）中表达，除了与各种病理状况有关外，还对血管系统发挥作用。本研究旨在探讨内脂素的功能作用及其对大鼠离体肠系膜小阻力动脉作用的潜在机制。本研究在大鼠肠系膜血管床分离的小阻力动脉环中进行。虽然内脂素孵育对去甲肾上腺素引起的肠系膜动脉环收缩反应没有显著改变，但内皮完整的环对乙酰胆碱的舒张反应明显减弱，而对硝普钠（SNP）的舒张反应没有改变。在去内皮化的标本中，内脂素对乙酰胆碱反应的抑制作用并不明显。用烟酰胺磷酸核糖基转移酶（NAMPT）抑制剂 FK866 或超氧化物歧化酶（SOD）孵育组织可逆转内脂素对乙酰胆碱舒张反应的抑制作用。与单独孵育 L-NAME 相比，内脂素与 Nω-硝基-L-精氨酸甲酯（L-NAME）共同孵育对乙酰胆碱引起的血管反应没有产生显著改变。肠系膜 PVAT 内脂素水平明显高于血浆内脂素水平，并呈正相关。我们的研究结果表明，内脂素诱导的大鼠离体小阻力动脉内皮依赖性舒张反应减弱是由氧自由基和一氧化氮（NO）生物利用度降低介导的。由于肥胖和体重过度增加等多种病理状况导致的全身性和/或局部内脂素水平升高，可能在血管功能障碍的发生和/或发展中起重要作用。
