Cardiovascular diseases: protective effects of melatonin

Tengattini, Sandra; Reíter, Russel J.; Tan, Dun Xian; Terrón, M. Pilar; Rodella, Luigi Fabrizio; Rezzani, Rita

doi:10.1111/j.1600-079x.2007.00518.x

Cited by 264 publications

(278 citation statements)

References 97 publications

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“…The activation of MT 1 in the rat caudal artery could lead to vasoconstriction, 17 but this action was not shown in other vessels, including the aorta. Receptormediated melatonin action in the aorta was suggested to enhance NO signaling 27 and upregulate antioxidant enzymes, 40 which may protect against increased ROS and consequent aorta stiffness, which is increased after the inhibition of NO synthase in rats. 41 The exact localization of receptors in different aorta layers, together with the determination of MT 2 density and changes in MT 1 /MT 2 ratio are needed to clarify the physiological role of melatonin in the aorta.…”

Section: Discussionmentioning

confidence: 99%

Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats

et al. 2009

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Melatonin plays a role in blood pressure (BP) control. The aim of this study was to determine whether melatonin concentrations and melatonin receptor levels are altered in L-NAME-treated, NO-deficient hypertensive rats. Two groups of male adult Wistar rats were investigated: rats (n¼36) treated with NO-synthase inhibitor L-NAME (40 mg kg À1 ) and age-matched controls (n¼36). BP was measured weekly by tail-cuff plethysmography. After 4 weeks, L-NAME administration increased BP (178±1 vs. control 118 ± 1 mm Hg). At the end of treatment, rats were killed in regular 4 h intervals over a 24-h period. Melatonin concentrations in the plasma, pineal gland, heart and kidney and melatonin receptor (MT 1 ) density in the aorta were determined. A significant daily rhythm of melatonin concentrations was found in the blood, pineal gland, kidney and heart of both control and hypertensive rats. Peak nighttime pineal melatonin concentrations were higher in L-NAME-treated rats than in controls (3.38 ± 0.48 vs. 1.75 ± 0.33 ng per pineal gland). No differences between both groups were found in melatonin concentrations in blood, kidney and heart or in the MT 1 receptor density in the aorta. Our results suggest that L-NAME treatment enhances melatonin production in the pineal gland, potentially by decreasing an inhibitory effect of NO on melatonin production in the pineal gland. However, the enhanced pineal melatonin formation was insufficient to increase melatonin concentrations in circulation, heart and kidney of L-NAME-treated rats, indicating an increased use of melatonin in hypertensive animals. INTRODUCTIONMelatonin is a hormone produced by the pineal gland in a circadian manner and exhibits a broad spectrum of effects, including those in the cardiovascular system. Melatonin has been suggested to play a role in blood pressure (BP) control. Earlier reports have shown that pinealectomized rats developed hypertension, 1 and the administration of melatonin in this model normalized the increased BP. 2 Melatonin decreased BP in hypertensive patients, 3 and the addition of melatonin to antihypertensive medication in patients with nocturnal hypertension reduced nighttime systolic BP. 4 However, the mechanisms behind melatonin's effect on BP are still not completely understood.The hypotensive effect of melatonin could be mediated either by a direct effect on vessels or by decreasing brain serotonin release, resulting in sympathetic inhibition or parasympathetic stimulation. 5 There are rather limited data about changes of melatonin concentrations related to essential hypertension in the literature. Plasma melatonin and urinary 6-sulfatoxymelatonin levels have been reported

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Section: Discussionmentioning

confidence: 99%

Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats

et al. 2009

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“…Melatonin has been demonstrated to be an efficient antioxidant with great clinical significance (3,22). In addition to its ADMAlowering effect (2), our data demonstrate that the beneficial effects of melatonin include enhancement of tissue l-arginine levels and its action as a PKC inhibitor.…”

Section: Melatonin Regulates Pkc In Bdl Ratsmentioning

confidence: 60%

Melatonin regulates L-arginine transport and NADPH oxidase in young rats with bile duct ligation: role of protein kinase C

et al. 2013

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Background: Bile duct ligation (BDL) is a commonly used cholestatic liver disease (cLD) model. We recently found that l-arginine levels were significantly raised by melatonin in young rats with BDL. We hypothesized that protein kinase c-α (PKc-α) is involved in the increases of l-arginine in melatonintreated BDL rats. In addition, we tested whether melatonin prevents nicotinamide adenine dinucleotide phosphate (NADPh) oxidase-induced reactive oxygen species (ROs) production, in rats with BDL, through PKc. Methods: Four groups of young male rats were studied: shams (n = 6), untreated BDL rats (n = 9), melatonin-treated shams (n = 6, M), and melatonin-treated BDL rats (n = 6, BDL + M). Melatonin-treated rats received daily melatonin 1 mg/kg/d via i.p. injection. All surviving rats were killed 14 d after surgery. results: Melatonin prevented BDL-induced mortality and kidney injury. Melatonin additionally increased l-arginine concentrations in BDL liver, which is correlated with decreased PKc-α translocation. Next, melatonin increased l-arginine levels in BDL kidneys, which was correlated with decreased renal levels of arginase II. In the BDL kidney, melatonin decreased PKc-β translocation, reduced p47phox translocation, and diminished NADPh-dependent superoxide production. conclusion: Melatonin inhibits PKc-α to increase cationic amino acid transporter-1 (cAT-1)-mediated l-arginine uptake in BDL liver, whereas it inhibits PKc-β to reduce NADPhdependent superoxide production.

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“…For example, an infusion of melatonin to genetically hypercholesterolemic rats decreased cholesterol levels in plasma and favored an involution of steatohepatosis, 65 although the cholesterol decrease may have been related to greater renal excretion. 66 In rats fed fructose, which causes changes characteristic of the metabolic syndrome, melatonin attenuated deterioration of the lipid blood profile in a dose-dependent manner. 67 Two different dose levels of melatonin significantly decreased lipid peroxidation and levels of cholesterol, phospholipids, triglycerides, and free fatty acids in rat brain and liver.…”

Section: Effect Of Melatonin On Lipidsmentioning

confidence: 99%

Melatonin and its use in atherosclerosis and dyslipidemia

Danilenko¹,

Ragino²

2013

CPT

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A review of pineal melatonin synthesis, regulation, and physiological effects indicates that not only does melatonin act as a hormonal signal of darkness, but also that it possesses antioxidant and anti-inflammatory properties. Although oxidation and inflammation play a pivotal role in atherogenesis, no studies have investigated administration of melatonin for human arterial atherosclerosis. However, 13 clinical trials have investigated use of melatonin in dyslipidemia, which is a close correlate of atherosclerosis. The results of these clinical trials, particularly the five that are placebo-controlled, are inconclusive as to whether melatonin can normalize the blood lipid profile. Significant confounders in these studies might be a phase shift of the cholesterol rhythm by melatonin, a posture effect at venipuncture, uncontrolled diet during the course of melatonin intake, and the phenomenon of regression to the mean. Thus, future studies are required, which should also consider use of higher doses of melatonin and/or measurement of oxidized forms of cholesterol-containing particles (which are the most aggressive in relation to atherogenesis) in addition to lipidic fractions.

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Cardiovascular diseases: protective effects of melatonin

Cited by 264 publications

References 97 publications

Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats

Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats

Melatonin regulates L-arginine transport and NADPH oxidase in young rats with bile duct ligation: role of protein kinase C

Melatonin and its use in atherosclerosis and dyslipidemia

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