Melatonin ameliorates endothelial dysfunction, vascular inflammation, and systemic hypertension in rats with chronic intermittent hypoxia

Hung, Ming-Wai; Kravtsov, Gennadi M.; Lau, Chi-Fai; Poon, A.M.S.; Tipoe, George L.; Fung, Man-Lung

doi:10.1111/jpi.12067

Cited by 91 publications

(74 citation statements)

References 63 publications

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“…Rats exposed to IH over 3 weeks developed systemic hypertension and increased markers of aortic inflammation and oxidative stress. Remarkably, the hypertension and inflammation was almost completely abolished by melatonin, and authors ascribed these findings to the possible hypoxic suppression of pineal melatonin synthesis [122] and to the anti-oxidant properties of melatonin [123]. Totoson et al examined whether cardiovascular effects of IH could be prevented by treatment with a statin, since these drugs are known to have anti-inflammatory effects.…”

Section: Osa and Inflammation: Animal/cell Studiesmentioning

confidence: 99%

Inflammation in sleep apnea: An update

Unnikrishnan

Jun

Polotsky

2014

Rev Endocr Metab Disord

177

118

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Obstructive sleep apnea (OSA) is a common disorder associated with cardiovascular disease (CVD). One theory to explain this relationship proposes that OSA can induce systemic inflammation, thereby inducing CVD. This theory is based on the premise that obesity is a pro-inflammatory state, and that physiological derangements during sleep in subjects with OSA further aggravate inflammation. In support of this theory, some clinical studies have shown elevated inflammatory biomarkers in OSA subjects, or improvement in these markers following treatment of OSA. However, the data are inconsistent and often confounded by the effects of comorbid obesity. Animal models of OSA have been developed, which involve exposure of rodents or cells to intermittent hypoxia, a hallmark feature of OSA. Several of these experiments demonstrate that intermittent hypoxia can stimulate inflammatory pathways and lead to cardiovascular or metabolic pathology. In this review, we review relationships between OSA and inflammation, with particular attention to studies published within the last year.

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Section: Osa and Inflammation: Animal/cell Studiesmentioning

confidence: 99%

Inflammation in sleep apnea: An update

Unnikrishnan

Jun

Polotsky

2014

Rev Endocr Metab Disord

177

118

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“…Other natural compounds (e.g. melatonin and resveratrol) are known to rescue vascular dysfunctions by the inhibition of NADPH oxidase, a major source of ROS, and the activity of antioxidant enzymes such as Cu,Zn SOD, catalase and GSH peroxidase [147,148,149]. …”

Section: Role Of Copper Transport Systems During Angiogenesismentioning

confidence: 99%

Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems

Urso

Maffia²

2015

J Vasc Res

129

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Angiogenesis critically sustains the progression of both physiological and pathological processes. Copper behaves as an obligatory co-factor throughout the angiogenic signalling cascades, so much so that a deficiency causes neovascularization to abate. Moreover, the progress of several angiogenic pathologies (e.g. diabetes, cardiac hypertrophy and ischaemia) can be tracked by measuring serum copper levels, which are being increasingly investigated as a useful prognostic marker. Accordingly, the therapeutic modulation of body copper has been proven effective in rescuing the pathological angiogenic dysfunctions underlying several disease states. Vascular copper transport systems profoundly influence the activation and execution of angiogenesis, acting as multi-functional regulators of apparently discrete pro-angiogenic pathways. This review concerns the complex relationship among copper-dependent angiogenic factors, copper transporters and common pathological conditions, with an unusual accent on the multi-faceted involvement of the proteins handling vascular copper. Functions regulated by the major copper transport proteins (CTR1 importer, ATP7A efflux pump and metallo-chaperones) include the modulation of endothelial migration and vascular superoxide, known to activate angiogenesis within a narrow concentration range. The potential contribution of prion protein, a controversial regulator of copper homeostasis, is discussed, even though its angiogenic involvement seems to be mainly associated with the modulation of endothelial motility and permeability.

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“…This assumption was confirmed as melatonin promoted a decrease in systolic BP and prevented endothelial dysfunction with ameliorated levels of nitric oxide, endothelial-dependent relaxation, and expressions of eNOS and antioxidant enzymes (Hung et al, 2013). …”

Section: What Is Already Known Concerning the Efficacy Of Ahds?mentioning

confidence: 86%

The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

Diogo

Monteiro

2014

Front. Physiol.

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Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT.

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Melatonin ameliorates endothelial dysfunction, vascular inflammation, and systemic hypertension in rats with chronic intermittent hypoxia

Cited by 91 publications

References 63 publications

Inflammation in sleep apnea: An update

Inflammation in sleep apnea: An update

Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems

The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

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