# In Vitro Effects of Fentanyl on Aortic Viscoelasticity in a Rat Model of Melatonin Deficiency

## TL;DR

This study examines how fentanyl affects aortic stiffness in rats with low melatonin levels, finding complex interactions that suggest non-opioid mechanisms.

## Contribution

The study reveals that fentanyl's effects on aortic viscoelasticity in melatonin-deficient rats are not opioid-related and vary with melatonin status.

## Key findings

- Fentanyl combined with melatonin deficiency increased aortic stiffness in rats.
- Fentanyl alone decreased aortic stiffness in both melatonin-deficient and normal rats.
- Naloxone reduced aortic stiffness in normal rats but did not block fentanyl's effects.

## Abstract

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 10−9 M fentanyl, the pin increased the natural frequency (f0) and modulus of elasticity (E’) compared to the sham-operated. Independently, fentanyl treatment decreased f0 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.