Long-term Mercury Exposure Accelerates the Development of Hypertension in Prehypertensive Spontaneously Hypertensive Rats Inducing Endothelial Dysfunction: the Role of Oxidative Stress and Cyclooxygenase-2

Simões, Rakel Passos; Fardin, P; Vassallo, Dalton Valentim; Padilha, Alessandra Simão

doi:10.1007/s12011-019-01952-8

Cited by 11 publications

(5 citation statements)

References 45 publications

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“…To investigate whether the cardiac effects were not due to other factors, such as vascular effects leading to pressure overload, we tested the copper effects on aortic segments. As the aorta is a vessel that readily re ects the effects of metals producing oxidative stress [33][34][35], the fact that these three doses did not alter vascular reactivity reinforces the idea that the effects found in this study are restricted to the heart only. Therefore, we did not proceed with any vascular studies because no changes were found.…”

Section: Discussionsupporting

confidence: 77%

Cardiovascular Harmful Effects of Recommended Daily Doses (13 µg/kg/day), Tolerable Upper Intake Doses (0.14 mg/kg/day) and Twice the Tolerable Doses (0.28 mg/kg/day) of Copper

et al. 2023

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Copper is essential for homeostasis and regulation of body functions, but in excess, it is a cardiovascular risk factor since it increases oxidative stress. The objective of this study was to evaluate the effects of exposure to the recommended daily dose (13 µg/kg/day), upper tolerable dose (0.14 mg/kg/day) and twice the upper tolerable dose (0.28 mg/kg/day) via i.p. over 4 weeks on the vascular reactivity of aortic rings and the contraction of LV papillary muscles. It was also determined whether the antioxidant peptide from egg white hydrolysate (EWH) prevents these effects. Copper exposure at the doses evaluated did not change weight gain, the reactivity of the aortic rings or the cardiac mass. The dose of 0.13 µg/kg/day did not reduce the force of contraction, but it impaired the time derivatives of force. Doses of 0.14 and 0.28 mg/kg/day reduced the force of contraction, the inotropic response to calcium and isoproterenol, the postrest contraction and the peak and plateau of tetanized contractions. EWH treatment antagonized these effects. These results suggest that copper, even at the dose described as upper tolerable, can impair cardiac contraction without altering vascular reactivity. Antioxidative stress therapy with EWH reversed these harmful effects, suggesting a possible strategy for the amelioration of these effects.

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Section: Discussionsupporting

confidence: 77%

Cardiovascular Harmful Effects of Recommended Daily Doses (13 µg/kg/day), Tolerable Upper Intake Doses (0.14 mg/kg/day) and Twice the Tolerable Doses (0.28 mg/kg/day) of Copper

et al. 2023

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“…The organism contains multiple antioxidant defense mechanisms, which keep oxidative stress to the appropriate levels. Regarding superoxide anion, the main enzyme responsible for its physiological metabolism is SOD, the activity and expression of which are reduced in the cardiovascular system in hypertension [86,87]. Regarding several studies, manipulation of gut microbiota with different approaches, including supplementation with synbiotics and probiotics, restored these alterations [88][89][90].…”

Section: Discussionmentioning

confidence: 99%

Supplementation with the Symbiotic Formulation Prodefen® Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats

et al. 2022

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In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen® (108 colony forming units/day, 4 weeks). Prodefen® diminished systolic blood pressure and serum endotoxin, as well as the vasoconstriction elicited by electrical field stimulation (EFS), and enhanced acetic and butyric acid in fecal samples, and the vasodilation induced by the exogenous NO donor DEA-NO. Unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in rats supplemented with Prodefen®. Both neuronal NO release and neuronal NOS activity were enhanced by Prodefen®, through a hyperactivation of protein kinase (PK)A, PKC and phosphatidylinositol 3 kinase-AKT signaling pathways. The superoxide anion scavenger tempol increased both NO release and DEA-NO vasodilation only in control animals. Prodefen® caused an increase in both nuclear erythroid related factor 2 and superoxide dismutase activities, consequently reducing both superoxide anion and peroxynitrite releases. In summary, Prodefen® could be an interesting non-pharmacological approach to ameliorate hypertension.

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“…Previous studies showed that exposure to low concentrations of Hg leads to vascular injury following the increase in peripheral vascular resistance that is associated with a higher risk of mortality (Lemos et al, 2012;Fardin et al, 2019;Simões et al, 2020;Ronchetti et al, 2022). Moreover, the increase of mortality in animals exposed to Hg may be associated with Hg binding to thiol groups of cardiac proteins, inducing maladaptive changes in channels that influence the action potentials and cardiac rhythm (Oliveira et al, 2019;Vassallo et al, 2019).…”

Section: Association Between Arrhythmias and Rosmentioning

confidence: 99%

Chronic exposure to mercury increases arrhythmia and mortality post-acute myocardial infarction in rats

Bello,

Wilke,

Simões

et al. 2023

Front. Physiol.

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Introduction: Mercury (Hg) is a heavy metal that causes a variety of toxic effects in eukaryotic cells. Previous studies have reported detrimental effects of mercury toxicity in the cardiovascular system. Given the importance of understanding the relationship between Hg and cardiovascular disease, we sought to investigate if the Hg could worsen the myocardial repercussions following ischemic injury. We demonstrated that once mercury toxicity is established, it can influence the outcome of myocardial infarction (MI).Methods: Male Wistar rats received intramuscular injections of either saline (NaCl 0.9%) or mercuric chloride (HgCl2, first dose of 4.6 μg/kg, and subsequent doses of 0.07 μg/kg/day) for 4 weeks. Three weeks post-exposure, we induced transmural infarction in the left ventricle free wall through coronary artery occlusion surgery. Results: ECG recordings obtained from MI groups demonstrated alterations in the rhythm of the heartbeat/heart electrical activity, as expected, including ventricular extrasystoles and ventricular tachycardia. However, the MI group exposed to Hg (MI-Hg) exhibited augmented ventricular extrasystoles and ventricular tachycardia compared to the MI group. Also, Basckó coefficient revealed that the arrhythmic events—after MI—were aggravated by Hg exposure.Discussion: Our results indicate that the significantly increased mortality in MI-Hg groups when compared to MI (21%, MI vs 32%, MI-Hg) is correlated with greater occurrence of arrhythmias. In conclusion, this study further supports the idea that exposure to mercury (Hg) should be recognized as a significant risk factor that exacerbates the impact of cardiac ischemic injury, potentially leading to an increased mortality rate among patients experiencing acute MI.

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Long-term Mercury Exposure Accelerates the Development of Hypertension in Prehypertensive Spontaneously Hypertensive Rats Inducing Endothelial Dysfunction: the Role of Oxidative Stress and Cyclooxygenase-2

Cited by 11 publications

References 45 publications

Cardiovascular Harmful Effects of Recommended Daily Doses (13 µg/kg/day), Tolerable Upper Intake Doses (0.14 mg/kg/day) and Twice the Tolerable Doses (0.28 mg/kg/day) of Copper

Cardiovascular Harmful Effects of Recommended Daily Doses (13 µg/kg/day), Tolerable Upper Intake Doses (0.14 mg/kg/day) and Twice the Tolerable Doses (0.28 mg/kg/day) of Copper

Supplementation with the Symbiotic Formulation Prodefen® Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats

Chronic exposure to mercury increases arrhythmia and mortality post-acute myocardial infarction in rats

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