The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension

Pecháňová, Oľga; Zicha, Josef; Paulis, Ludovít; Zenebe, Woineshet J.; Dobešová, Z; Kojsová, Stanislava; Jendeková, Lýdia; Sladkova, Martina; Dovinová, Ima; Šimko, Fedor; Kuneš, Jaroslav

doi:10.1016/j.ejphar.2007.01.035

Cited by 81 publications

(60 citation statements)

References 43 publications

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“…23 The administration of melatonin reduces BP and infarct size in rats with L-NAME induced hypertension in a regressive experimental setting, 24 as well as when melatonin administration started simultaneously with L-NAME treatment and before hypertension development. 25 The antihypertensive effect of melatonin was reduced compared with spontaneously hypertensive rats, 26 suggesting that the inhibited NO production by L-NAME reduces the hypotensive effect of melatonin. Melatonin can attenuate an increased BP by interfering with several control systems, such as the sympathetic nervous system, the NO-cGMP pathway 27 and the excessive production of ROS.…”

Section: Discussionmentioning

confidence: 99%

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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%

“…26 Therefore, it is expected that the antioxidant activity of melatonin could contribute to its antihypertensive effects. 27 The melatonin rhythm showed maximal levels during the night in the tissue of both the heart and the kidney.…”

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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“…In rats, pinealectomy results in the development of hypertension (Karppanen et al 1973;Zanoboni et al 1978) that in turn can be lowered by MEL treatment (Holmes and Sugden 1976). Likewise, MEL reduced BP in spontaneously hypertensive rats (Pechanova et al 2007), L-NAME (N(G)-nitro-L-arginine-methyl ester)-treated hypertensive rats (Paulis et al 2010), and in rats hypertensive as a result of high fructose diet (Leibowitz et al 2008) or due to stress (Xia et al 2008).…”

Section: Introductionmentioning

confidence: 98%

“…These include, on the one hand, non-specific mechanisms reflecting the strong antioxidant capacity of MEL and its metabolites ) that may preserve especially endothelial function and structure (Anwar et al 2001;Pechanova et al 2007), resulting in vasodilative and hypotensive effects. On the other hand, in mammals, MEL may influence BP also via two subtypes of G-protein-coupled plasma membrane receptors, MT 1 and MT 2 (Reppert et al 1994(Reppert et al , 1995Dubocovich et al 2010).…”

Section: Introductionmentioning

confidence: 99%

The Presence and Localization of Melatonin Receptors in the Rat Aorta

et al. 2011

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Melatonin is involved in blood pressure modulation in rats and humans. Some of the effects of melatonin are presumably mediated via two G-protein-coupled receptors (MT(1) and MT(2)), but the distribution of MT(1) and MT(2) in the cardiovascular system remains to be explored comprehensively. We investigated the expression of both the receptors in the rat aorta on mRNA level by RT-PCR and real time RT-PCR as well as on protein level via western blotting and immunofluorescence microscopy. We verified MT(1) mRNA expression in the rat aorta and demonstrated the absence of MT(2) mRNA in this vessel type. MT(1) receptors were confirmed also at the protein level, and surprisingly they were preferentially localized to the tunica adventitia. Since no daily changes in MT(1) mRNA expression were detected, we suppose that the circadian changes in circulating melatonin concentrations are sufficient to mediate circadian effects of melatonin in the aorta. The localization of MT(1) in the tunica adventitia suggests an influence of melatonin on vasa vasorum function and signal transduction in the aorta wall.

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“…27 Antioxidant properties of melatonin, which could participate in the mechanism of its antihypertensive effect, were demonstrated in experimental hypertension. 28 Anti-inflammatory actions of melatonin are related to the inhibition of prostaglandins effects, and, in particular, COX-2 downregulation. 29 Moreover, melatonin offers protection against fibrosis by preventing oxidative damage caused by lipid peroxidation and glutathione depletion.…”

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confidence: 99%

Effects of Melatonin and Pycnogenol on Small Artery Structure and Function in Spontaneously Hypertensive Rats

et al. 2010

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Abstract-It was suggested that oxidative stress has a key role in the development of endothelial dysfunction, as well as microvascular structural alterations. Therefore, we have investigated 2 substances with antioxidant properties: melatonin and Pycnogenol. We treated 7 spontaneously hypertensive rats (SHRs) with melatonin and 7 with Pycnogenol for 6 weeks. We compared results obtained with those observed in 7 SHRs and 7 Wistar-Kyoto normotensive control rats kept untreated. Mesenteric small resistance arteries were dissected and mounted on a wire myograph, and a concentrationresponse curve to acetylcholine was performed. Aortic contents of metalloproteinase 2, Bax, inducible NO synthase, and cyclooxygenase 2 were evaluated, together with the aortic content of total collagen and collagen subtypes and apoptosis rate. A small reduction in systolic blood pressure was observed. A significant improvement in mesenteric small resistance artery structure and endothelial function was observed in rats treated with Pycnogenol and melatonin. Total aortic collagen content was significantly greater in untreated SHRs compared with Wistar-Kyoto control rats, whereas a full normalization was observed in treated rats. Apoptosis rate was increased in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; an even more pronounced increase was observed in treated rats. Bax and metalloproteinase 2 expressions changed accordingly. Cyclooxygenase 2 and inducible NO synthase were more expressed in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; this pattern was normalized by both treatments. In conclusion, our data suggest that treatment with Pycnogenol and melatonin may protect the vasculature, partly independent of blood pressure reduction, probably through their antioxidant effects. Key Words: endothelial function Ⅲ melatonin Ⅲ Pycnogenol oxidative stress R eactive oxygen species (ROS) are generated as byproducts of cellular respiration and other metabolic processes and may contribute to oxidative damage. 1,2 The ROS family includes several molecules that have divergent effects on cellular function, namely, regulation of cell growth and differentiation, modulation of extracellular matrix production and breakdown, inactivation of NO, and stimulation of protein kinases and proinflammatory genes. 3-5 Importantly, some of these actions are associated with pathological changes in cardiovascular tissues. 6 In cardiovascular disease, increased ROS production leads to endothelial dysfunction, increased vascular contractility, vascular smooth muscle cell growth and apoptosis, monocyte migration, lipid peroxidation, inflammation, and increased deposition of extracellular matrix proteins, all processes contributing to vascular damage. 7 ROS may be important in the development and maintenance of hypertension, in terms of excess production of oxidants, decreased NO bioavailability, and decreased antioxidant capacity in the vasculature and kidneys. 6,7 Hypertension may contribute to structural and functional al...

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The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension

Cited by 81 publications

References 43 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

The Presence and Localization of Melatonin Receptors in the Rat Aorta

Effects of Melatonin and Pycnogenol on Small Artery Structure and Function in Spontaneously Hypertensive Rats

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