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Renal Dopamine Receptors and Oxidative Stress: Role in Hypertension.

ABSTRACT: Significance: The kidney plays an important role in the long-term control of blood pressure. Oxidative stress is one of the fundamental mechanisms responsible for the development of hypertension. Dopamine, via five subtypes of receptors, plays an important role in the control of blood pressure by various mechanisms, including the inhibition of oxidative stress. Recent Advances: Dopamine receptors exert their regulatory function to decrease the oxidative stress in the kidney and ultimately maintain normal sodium balance and blood pressure homeostasis. An aberration of this regulation may be involved in the pathogenesis of hypertension. Critical Issues: Our present article reviews the important role of oxidative stress and intrarenal dopaminergic system in the regulation of blood pressure, summarizes the current knowledge on renal dopamine receptor-mediated antioxidation, including decreasing reactive oxygen species production, inhibiting pro-oxidant enzyme nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, and stimulating antioxidative enzymes, and also discusses its underlying mechanisms, including the increased activity of G protein-coupled receptor kinase 4 (GRK4) and abnormal trafficking of renal dopamine receptors in hypertensive status. Future Directions: Identifying the mechanisms of renal dopamine receptors in the regulation of oxidative stress and their contribution to the pathogenesis of hypertension remains an important research focus. Increased understanding of the role of reciprocal regulation between renal dopamine receptors and oxidative stress in the regulation of blood pressure may give us novel insights into the pathogenesis of hypertension and provide a new treatment strategy for hypertension.

SUBMITTER: Yang J

PROVIDER: S-EPMC7910420 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Renal Dopamine Receptors and Oxidative Stress: Role in Hypertension.

Yang Jian J Villar Van Anthony M VAM Jose Pedro A PA Zeng Chunyu C

Antioxidants & redox signaling 20200529 9

Significance: The kidney plays an important role in the long-term control of blood pressure. Oxidative stress is one of the fundamental mechanisms responsible for the development of hypertension. Dopamine, via five subtypes of receptors, plays an important role in the control of blood pressure by various mechanisms, including the inhibition of oxidative stress. Recent Advances: Dopamine receptors exert their regulatory function to decrease the oxidative stress ...[more]

PMID: 32349533

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Project description:Mercury is an extremely dangerous environmental contaminant responsible for episodes of human intoxication throughout the world. Methylmercury, the most toxic compound of this metal, mainly targets the central nervous system, accumulating preferentially in cells of glial origin and causing oxidative stress. Despite studies demonstrating the current exposure of human populations, the consequences of mercury intoxication and concomitant use of drugs targeting the central nervous system (especially drugs used in long-term treatments, such as analgesics) are completely unknown. Morphine is a major option for pain management; its global consumption more than quadrupled in the last decade. Controversially, morphine has been proposed to function in oxidative stress independent of the activation of the opioid receptors. In this work, a therapeutic concentration of morphine partially protected the cellular viability of cells from a C6 glioma cell line exposed to methylmercury. Morphine treatment also reduced lipid peroxidation and totally prevented increases in nitrite levels in those cells. A mechanistic study revealed no alteration in sulfhydryl groups or direct scavenging at this opioid concentration. Interestingly, the opioid antagonist naloxone completely eliminated the protective effect of morphine against methylmercury intoxication, pointing to opioid receptors as the major contributor to this action. Taken together, the experiments in the current study provide the first demonstration that a therapeutic concentration of morphine is able to reduce methylmercury-induced oxidative damage and cell death by activating the opioid receptors. Thus, these receptors may be a promising pharmacological target for modulating the deleterious effects of mercury intoxication. Although additional studies are necessary, our results support the clinical safety of using this opioid in methylmercury-intoxicated patients, suggesting that normal analgesic doses could confer an additional degree of protection against the cytotoxicity of this xenobiotic.

Project description:Background: Hypertension is a major cause of mortality worldwide. The kidneys play a crucial role in regulating blood pressure and fluid volume. The relationship between the kidneys and hypertension is complex, involving factors such as the renin-angiotensin system, oxidative stress, and inflammation. This study aims to assess the levels of inflammatory markers, oxidative stress, and metabolic factors in the kidneys, focusing on their potential role in early renal damage and their association with the development of hypertension. Methods: This study was designed to compare the levels of selected inflammatory markers, e.g., interleukins, tumor necrosis factor-α (TNF-α), transforming growth factor, and serine/threonine-protein (mTOR); oxidative stress markers such as malondialdehyde, sulfhydryl group, and glucose (GLC); and metabolic markers among other enzymes, such as alanine transaminase (ALT), aspartate transaminase (AST), hexokinase II (HK-II), and hypoxia-inducible factor-1α (HIF-1α), as well as creatinine in the kidneys of spontaneously hypertensive rats (SHR/NCrl, n = 12) and Wistar Kyoto rats (WKY/NCrl, n = 12). Both juvenile (5 weeks old) and maturing (10 weeks old) specimens were examined using spectrophotometric methods, e.g., ELISA. Results: Juvenile SHRs exhibited reduced renal levels of all studied cytokines and chemokines, with lower oxidative stress and deficits in the mTOR and HK-II levels compared to the age-matched WKYs. Maturing SHRs showed increased renal levels of interleukin-1β (IL-1β), IL-6, IL-18, and TNF-α, alongside elevated carbonyl stress and increased HIF-1α as opposed to their control peers. The levels of all other studied markers were normalized in these animals, except for ALT (increased), ALP, and GLC (both reduced). Conclusions: This study underscores the significant impact of inflammatory, oxidative stress, and metabolic marker changes on renal function. Juvenile SHRs display lower marker levels, indicating an immature immune response and potential subclinical kidney damage that may contribute to hypertension development. In contrast, mature SHRs exhibit chronic inflammation, oxidative dysregulation, and metabolic disturbances, suggesting cellular damage. These changes create a feedback loop that worsens kidney function and accelerates hypertension progression, highlighting the kidneys' crucial role in both initiating and exacerbating this condition.

Project description:Background and aimsFetal undernutrition is a risk factor for heart disease in both genders, despite the protection of women against hypertension development. Using a rat model of maternal undernutrition (MUN) we aimed to assess possible sex differences in the development of cardiac alterations and the implication of hypertension and cardiac oxidative stress.MethodsMale and female offspring from rats fed ad libitum (control) or with 50% of the normal daily intake during the second half of gestation (MUN) were used. Heart weight/body weight ratio (HW/BW), hemodynamic parameters (anaesthetized rats) and plasma brain natriuretic peptide (BNP, ELISA) were assessed in 21-day, 6-month and 22-month old rats. Plasma testosterone (ELISA) and cardiac protein expression of enzymes related to reactive oxygen species synthesis (p22phox, xanthine-oxidase) and degradation (catalase, Cu/Zn-SOD, Mn-SOD, Ec-SOD) were evaluated in 21-day and 6-month old rats (Western Blot). Heart structure and function was studied at the age of 22 months (echocardiography).ResultsAt the age of 21 days MUN males exhibited significantly larger HW/BW and cardiac p22phox expression while females had reduced p22phox expression, compared to their respective sex-matched controls. At the age of 6-months, MUN males showed significantly larger blood pressure and cardiac xanthine-oxidase expression; MUN females were normotensive and had a lower cardiac expression of antioxidant enzymes, compared to their respective sex-matched controls. At the age of 22 months, both MUN males and females showed larger HW/BW and left ventricular mass and lower ejection fraction compared to sex-matched controls; only MUN males exhibited hypertension and a larger plasma BNP compared to aged male controls.Conclusions1) During perinatal life females exposed to fetal undernutrition are protected from cardiac alterations, but in ageing they exhibit ventricular hypertrophy and functional loss, like MUN males; 2) cardiac oxidative stress might be implicated in the observed heart alterations in both sexes and 3) the severity of cardiac damage might be greater in males due to hypertension.

Dataset Information

Renal Dopamine Receptors and Oxidative Stress: Role in Hypertension.

Publications

Renal Dopamine Receptors and Oxidative Stress: Role in Hypertension.

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