Department of Behavioral Neurobiology, Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Int J Mol Sci. 2024 May 23;25(11):5669. doi: 10.3390/ijms25115669.
Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency and to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity was estimated in strip preparations from pinealectomized (pin, melatonin deficiency) and sham-operated (sham, normal melatonin) adult rats using the forced oscillations method. In the untreated aortic wall pin, the viscoelasticity was not significantly altered. However, combined with 10 M fentanyl, the pin increased the natural frequency (f) and modulus of elasticity (E') compared to the sham-operated. Independently, fentanyl treatment decreased f and E' compared separately to untreated sham and pin preparations. The effects of fentanyl were neither dose-dependent nor affected by naloxone, suggesting a non-opioid mechanism. Furthermore, an independent effect of naloxone was also detected in the normal rat aortic wall, resulting in reduced E'. Additional studies are needed that may improve the clinical decisions for pain management and anesthesia for certain patients with co-occurring chronic low levels of blood plasma melatonin and some diseases.
褪黑素影响动脉生物力学,其缺乏可导致动脉壁重塑,导致僵硬度增加。先前也观察到芬太尼对主动脉壁的直接作用。本研究旨在评估褪黑素缺乏大鼠模型中芬太尼对主动脉粘弹性的体外影响,并验证褪黑素缺乏导致动脉壁僵硬度增加的假设。使用强迫振荡法在松果体切除(pin,褪黑素缺乏)和假手术(sham,正常褪黑素)成年大鼠的条带制剂中评估粘弹性。在未处理的主动脉壁 pin 中,粘弹性没有明显改变。然而,与 10 M 芬太尼联合使用时,与 sham 相比,pin 增加了自然频率 (f) 和弹性模量 (E')。独立地,芬太尼处理分别降低了未处理的 sham 和 pin 制剂的 f 和 E'。芬太尼的作用既不是剂量依赖性的,也不受纳洛酮影响,提示存在非阿片类机制。此外,在正常大鼠的主动脉壁中也检测到纳洛酮的独立作用,导致 E'降低。需要进一步的研究,这可能会改善某些同时存在慢性低水平血浆褪黑素和某些疾病的患者的疼痛管理和麻醉的临床决策。