Chronic hypoxia inhibits the antihypertensive effect of melatonin on pulmonary artery

Das, R; Balonan, Lino C; Ballard, HJ; Ho, Siu Lau

doi:10.1016/j.ijcard.2007.04.030

Cited by 22 publications

(11 citation statements)

References 33 publications

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“…This effect may be due to its vasodilator and/or antioxidant actions. Previous studies have shown that melatonin vasodilates different vascular beds, presumably by MT2 receptor [32,36,37,53]. Further, NO and˙O À 2 reaction (k~7 9 10 9 L/mol/s) produces peroxynitrite [54], diminishing NO bioavailability and thus its vasodilator capacity.…”

Section: Discussionmentioning

confidence: 99%

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Torres

Gonzaléz‐Candia

Montt

et al. 2015

Journal of Pineal Research

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Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial- and muscular-dependent pathways. This was associated with an enhanced nitric oxide-dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.

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Section: Discussionmentioning

confidence: 99%

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Torres

Gonzaléz‐Candia

Montt

et al. 2015

Journal of Pineal Research

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“…Consequently, the increase in eNOS activity could elevate the NO production and lower the pulmonary vasoconstriction, although the cardiac output and pulmonary vascular resistance were not determined in this study. In addition, the receptor-mediated effect of melatonin in pulmonary vessels may alter the vasoreactivity to ligands, although it could be relatively less because the antihypertensive effect of melatonin is known to be inhibited by chronic hypoxia [52]. …”

Section: Discussionmentioning

confidence: 99%

Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats

Hung

Yeung

Lau

et al. 2017

IJMS

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Chronic hypoxia induces pulmonary hypertension and vascular remodeling, which are clinically relevant to patients with chronic obstructive pulmonary disease (COPD) associated with a decreased level of nitric oxide (NO). Oxidative stress and inflammation play important roles in the pathophysiological processes in COPD. We examined the hypothesis that daily administration of melatonin (10 mg/kg) mitigates the pulmonary hypertension and vascular remodeling in chronically hypoxic rats. The right ventricular systolic pressure (RVSP) and the thickness of pulmonary arteriolar wall were measured from normoxic control, vehicle- and melatonin-treated hypoxic rats exposed to 10% O2 for 14 days. Levels of markers for oxidative stress (malondialdhyde) and inflammation (tumor necrosis factor-α (TNFα), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and the expressions of total endothelial NO synthase (eNOS) and phosphorylated eNOS at serine1177 (ser1177) were determined in the lung tissue. We found that the RVSP and the thickness of the arteriolar wall were significantly increased in the vehicle-treated hypoxic animals with elevated levels of malondialdhyde and mRNA expressions of the inflammatory mediators, when compared with the normoxic control. In addition, the phosphorylated eNOS (ser1177) level was significantly decreased, despite an increased eNOS expression in the vehicle-treated hypoxic group. Melatonin treatment significantly attenuated the levels of RVSP, thickness of the arteriolar wall, oxidative and inflammatory markers in the hypoxic animals with a marked increase in the eNOS phosphorylation in the lung. These results suggest that melatonin attenuates pulmonary hypertension by antagonizing the oxidative injury and restoration of NO production.

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“…Elderly patients typically have reduced melatonin blood levels [21,[25][26][27]. Moreover, in patients suffering from primary hypertension decreased levels of melatonin were observed compared with normotensive patients [28]. Patients suffering from coronary heart disease, the most typical complication of chronic hypertension, demonstrated over fivefold lower level of serum melatonin at night compared with the control group [29].…”

Section: Discussionmentioning

confidence: 99%

Antioxidative effects of melatonin administration in elderly primary essential hypertension patients

Kędziora–Kornatowska

Szewczyk-Golec

Czuczejko

et al. 2008

Journal of Pineal Research

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The imbalance of the redox state of the aging organism may be involved in the development of primary essential hypertension. Melatonin, a potent antioxidant agent, was found to exert a hypotensive effect and improve the function of the cardiovascular system. The aim of this study was to determine the influence of melatonin supplementation on oxidative stress parameters in elderly primary essential hypertensive (EH) patients, controlled by a diuretic (indapamide) monotherapy. The levels of malondialdehyde (MDA) and reduced glutathione (GSH), activities of Cu-Zn superoxide dismutase (SOD-1), catalase (CAT) and glutathione peroxidase (GSH-Px) in erythrocytes, the plasma level of nitrate/nitrite, the content of carbonyl groups of plasma proteins and morning melatonin levels in the serum of 17 elderly EH patients were determined at the baseline and after the 15th and 30th days of melatonin supplementation (5 mg daily). Melatonin administration resulted in a significant increase in the morning melatonin concentration, SOD-1 and CAT activities, and a reduction in the MDA level. Statistically significant alterations in the levels of GSH, nitrate/nitrite and carbonyl groups and the activity of GSH-Px were not observed. These results indicate an improvement in the antioxidative defense of the organism by melatonin supplementation in the examined group and may suggest melatonin supplementation as an additional treatment supporting hypotensive therapy in elderly EH patients.

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Chronic hypoxia inhibits the antihypertensive effect of melatonin on pulmonary artery

Cited by 22 publications

References 33 publications

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats

Antioxidative effects of melatonin administration in elderly primary essential hypertension patients

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