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The MT1, but not MT2, gene is expressed in mesenteric artery (MA) and perivascular adipose tissue (PVAT) derived from MA (MA-PVAT). a RT-PCR analysis of MT1 mRNA expression in MA, MA-PVAT, and eye. Total RNA isolated from rat tissues was subjected to RT-PCR using specific primers for MT1 (316 bp) cDNA. Non-reversely transcribed samples (-RT, RNA instead of cDNA) and negative controls (PCR-neg.co, water instead of cDNA; RT-neg.co, water instead of RNA) are also shown. b RT-PCR analysis of MT2 mRNA expression in MA, PVAT derived from MA (MA-PVAT), and eye. Total RNA isolated from rat tissues was subjected to RT-PCR using specific primers for MT2 (390 bp; nested PCR, upper panel) and β-actin (496 bp; ACTB, lower panel) cDNAs. Two individual samples per tissue are shown. c Relative gene expression levels of MT1 in rat MA (n = 6) and PVAT derived from MA (MA-PVAT, n = 5). The experiments were carried out in technical triplicates for each sample. The distribution of data is displayed by box plots. The box represents the range from the first to third quartiles; the band near the middle of the box is the median, and the lines above and below the box indicate the locations of the minimum and maximum value. The asterisk indicates a significant difference (p < 0.05)
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Melatonin is released by the pineal gland and can modulate cardiovascular system function via the G protein-coupled melatonin receptors MT1 and MT2. Most vessels are surrounded by perivascular adipose tissue (PVAT), which affects their contractility. The aim of our study was to evaluate mRNA and protein expression of MT1 and MT2 in the mesenteric a...
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... Besides, the vascular effects of MEL are presumably mediated via two GPCRs named MT1 and MT receptors (Cecon et al. 2018). Furthermore, according to a number of studies, vascular MT1 receptors cause vasoconstriction, but MT2 receptors expressed in VSMCs cause vasodilation (Molcan et al. 2021). Likewise, ramelteon (RAM), specifically activates both MEL receptors (Erland et al. 2022). ...
... accompanied by enhanced antioxidant performance (Zarezadeh et al. 2022). Moreover, the accumulating evidence suggests that the presence of the MT1 receptor in perivascular adipose tissue can enhance the relaxation of VSMCs by releasing perivascular adipose tissue-derived relaxing factors (Molcan et al. 2021). Furthermore, prostaglandins, which are produced by cyclooxygenases (COX-1 and COX-2), play an important role in the contractile response under vasoconstrictive substances impact (Reis Costa et al. 2022) through the synthesis and release of endogenous vasodilators, including prostacyclin (PGI2) and epoxyeicosatrienoic Fig. 8 Shows the response of the aortas to stimulation by angiotensin II with endothelium from DM rats. ...
The current study explored melatonin (MEL) and its receptors, including MEL type 1 receptor (MT1) receptor and MEL type 2 receptor (MT2), along with the angiotensin-converting enzyme 2 (ACE2), influence on vascular responses to angiotensin II (Ang II) in rat aortic segments of normal and diabetic rats. The isolated aortic segments were exposed to MEL, the MEL agonist; ramelteon (RAM), the MEL antagonist; luzindole (LUZ), and an ACE2 inhibitor (S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3 H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid,) on Ang II-induced contractions in non-diabetic normal endothelium (non-DM E+), non-diabetic removed endothelium (non-DM E-), and streptozotocin-induced diabetic endothelium-intact (STZ-induced DM E+) rat aortic segments, as well as their combination in STZ-induced DM E + segments, were also included. The current results showed that MEL and RAM shifted Ang II dose-response curve (DRC) to the right side in non-DM E + and non-DM E- aorta but not in STZ-induced DM E + aorta. However, ACE2 inhibition abolished Ang II degradation only in STZ-induced DM E + segments, not in non-DM E + segments. Additionally, the combinations of MEL-LUZ and RAM-ACE2 inhibitor caused a rightward shift in Ang II response in STZ-induced DM E + segments, while the MEL-LUZ combination decreased Ang II DRC. The findings suggest that the effects of MEL and ACE2 inhibitor on Ang II responses depend on the condition of the endothelium and the distribution of the MEL receptors.
... Melatonin MT 1 receptors have been found in rat mesenteric artery's adventitia and media layers [49,50]. Only the MT 1 type has been confirmed in rat aorta, where these receptors have been detected at mRNA and protein levels predominantly in the outermost layer-the tunica adventitia [50]. ...
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.
... Melatonin MT1 receptors have been found in rat mesenteric artery's adventitia and media layers [50,51]. Only the MT1 type has been confirmed in rat aorta, where these receptors have been detected at mRNA and protein levels predominantly in the outermost layer -the tunica adventitia [51]. ...
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. It also aimed to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity of the aortic wall was estimated in strip preparations from pinealectomised and sham-operated adult rats using the forced oscillations method. We found that melatonin deficiency in the untreated aortic wall did not significantly alter viscoelasticity. However, combined with 10-9 M fentanyl, melatonin deficiency increased the natural frequency and arterial stiffness compared to the sham-operated. Independently, fentanyl treatment decreased the natural frequency and arterial stiffness compared separately to untreated normal and melatonin-deficient preparations. The observed 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 arterial stiffness. Further studies are needed to clarify the underlying mechanisms, which may improve the clinical decisions for pain management and anesthesia.
The hypotensive effects of melatonin are based on a negative correlation between melatonin levels and blood pressure in humans. However, there is a positive correlation in nocturnal animals that are often used as experimental models in cardiovascular research, and the hypotensive effects and mechanism of melatonin action are often investigated in rats and mice. In rats, the hypotensive effects of melatonin have been studied in normotensive and spontaneously or experimentally induced hypertensive strains. In experimental animals, blood pressure is often measured indirectly during the light (passive) phase of the day by tail-cuff plethysmography, which has limitations regarding data quality and animal well-being compared to telemetry. Melatonin is administered to rats in drinking water, subcutaneously, intraperitoneally, or microinjected into specific brain areas at different times. Experimental data show that the hypotensive effects of melatonin depend on the experimental animal model, blood pressure measurement technique, and the route, time and duration of melatonin administration. The hypotensive effects of melatonin may be mediated through specific membrane G-coupled receptors located in the heart and arteries. Due to melatonin’s lipophilic nature, its potential hypotensive effects can interfere with various regulatory mechanisms, such as nitric oxide and reactive oxygen species production and activation of the autonomic nervous and circadian systems. Based on the research conducted on rats, the cardiovascular effects of melatonin are modulatory, delayed, and indirect. Does melatonin have blood pressure-lowering effects, and are nocturnal animals suitable for testing the hypotensive effects of melatonin? The hypotensive effects of melatonin depend on the experimental animal model, blood pressure measurement method, route, time and duration of melatonin administration.
Melatonin is a simple compound with a proper chemical name N-acetyl-5-methoxy tryptamine and known as a hormone controlling circadian rhythm. Humans produce melatonin at night which is the reason for sleeping in the night and awakening over the day. Melatonin interacts with melatonin receptors MT1 and MT2 but it was also revealed that melatonin is a strong antioxidant and it also has a role in regulation of cell cycle. Currently, melatonin is used as a drug for some types of sleep disorder but the recent research points to the fact that melatonin can also serve for the other purposes including prophylaxis or therapy of lifestyle diseases, cancer, neurodegenerative disorders and exposure to chemicals. This review summarizes basic facts and direction of the current research on melatonin. The actual literature was scrutinized for the purpose of this review.
