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Metabolites
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Altered Metabolism Associated with Hypertension—a New Option for Drug Therapy?
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Altered Metabolism Associated with Hypertension—a New Option for Drug Therapy?

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Pharmacology and Drug Metabolism".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 17251

Special Issue Editors

Dr. Monika Kubacka

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Guest Editor
Department of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna Street, PL 30-688 Krakow, Poland
Interests: searching for new mechanisms of action of small molecules to treat hypertension and metabolic syndrome; inflammation and insulin signaling; obesity; adipose tissue; endothelial integrity; endothelial dysfunction; arterioscerosis; platelet aggregation; ligands of adrenergic, histamine, serotonin, and cannabinoid receptors; isolated organ studies
Special Issues, Collections and Topics in MDPI journals
Dr. Magdalena Kotańska

E-Mail Website
Guest Editor
Department of Pharmacological Screening, Jagiellonian University Medical College, 9 Medyczna Street, PL 30-688 Krakow, Poland
Interests: searching for new mechanisms of action of small molecules to reduce body mass or compensating for disorders of the circulatory system or leveling depression-like disorders; pharmacology developments towards new therapeutic approaches for obesity, diabetes and selected metabolic disorders, hypertension, atherosclerosis, depression; ligands of adrenergic, histamine, serotonin, adenosine and cannabinoid receptors
Special Issues, Collections and Topics in MDPI journals
Dr. Marek Bednarski

E-Mail
Guest Editor
Department of Pharmacological Screening,, Medical College, Jagiellonian University, 9 Medyczna Street, PL 30-688 Krakow, Poland
Interests: searching for new mechanisms of action of small molecules to treat hypertension and metabolic syndrome, rhythym disturbances, endothelial dysfunction, and oxidative stress; ligands of adrenergic, histamine, dopamine, and serotonin receptors; isolated organ studies; telemetry monitoring of cardiovascular system

Special Issue Information

Dear Colleagues,

Many people in today’s world, are suffering from metabolic syndrome, obesity or hypertension, which, together with decreased physical activity, may lead to cardiovascular disease with fatal consequences. Even the current COVID-19 pandemic might contribute to a significant increase in incidence of metabolic syndrome as well as associated complications. Therefore, the search for new and better therapeutic approaches targeting altered endogenous metabolism is necessary.

Essential hypertension is a multifactorial disorder, which means that various central and peripheral mechanisms contribute to increasing blood pressure. Altered metabolism—seen in, for example, obesity—is associated with endothelial, renal and hepatic dysfunction, which may explain in part the development of hypertension. The currently available antihypertensive drugs have proven effective in reducing blood pressure; however, beyond hypertension, in some cases, they have failed to treat end-target organ injury or restore metabolic imbalance. The discovery of mechanisms regulating metabolism may lead to novel strategies and therapies for altered metabolism and hypertension.

The observations show that research into physiological mechanisms and different pharmacological interventions impacting altered metabolism and hypertension are fascinating and can also be beneficial in clinical conditions. The search for new and better therapeutic targets in the treatment of both hypertension and altered metabolism, as well as specific small molecules that affect these targets, is especially needed. Research in identifying metabolites associated with hypertension and altered metabolism will also be highly appreciated. This Special Issue of Metabolites invites both reviews and original articles covering the latest developments in altered endogenous metabolism/metabolites and hypertension. Papers on the interaction between hypertension and altered metabolism will be considered particularly valuable.

Dr. Monika Kubacka
Dr. Magdalena Kotańska
Dr. Marek Bednarski
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hypertension
  • metabolism
  • antihypertensive therapy
  • end organ damage
  • obesity
  • insulin resistance
  • oxidative stress

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Published Papers (5 papers)

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Research

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26 pages, 7350 KiB  
Article
Manifestations of Liver Impairment and the Effects of MH-76, a Non-Quinazoline α1-Adrenoceptor Antagonist, and Prazosin on Liver Tissue in Fructose-Induced Metabolic Syndrome
by Monika Kubacka, Barbara Nowak, Monika Zadrożna, Małgorzata Szafarz, Gniewomir Latacz, Henryk Marona, Jacek Sapa, Szczepan Mogilski, Marek Bednarski and Magdalena Kotańska
Metabolites 2023, 13(11), 1130; https://doi.org/10.3390/metabo13111130 - 3 Nov 2023
Viewed by 1456
Abstract
Excessive fructose consumption may lead to metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD) and hypertension. α1-adrenoceptors antagonists are antihypertensive agents that exert mild beneficial effects on the metabolic profile in hypertensive patients. However, they are no longer used as a first-line therapy [...] Read more.
Excessive fructose consumption may lead to metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD) and hypertension. α1-adrenoceptors antagonists are antihypertensive agents that exert mild beneficial effects on the metabolic profile in hypertensive patients. However, they are no longer used as a first-line therapy for hypertension based on Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) outcomes. Later studies have shown that quinazoline-based α1-adrenolytics (prazosin, doxazosin) induce apoptosis; however, this effect was independent of α1-adrenoceptor blockade and was associated with the presence of quinazoline moiety. Recent studies showed that α1-adrenoceptors antagonists may reduce mortality in COVID-19 patients due to anti-inflammatory properties. MH-76 (1-[3-(2,6-dimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride)) is a non-quinazoline α1-adrenoceptor antagonist which, in fructose-fed rats, exerted anti-inflammatory, antihypertensive properties and reduced insulin resistance and visceral adiposity. In this study, we aimed to evaluate the effect of fructose consumption and treatment with α1-adrenoceptor antagonists of different classes (MH-76 and prazosin) on liver tissue of fructose-fed rats. Livers were collected from four groups (Control, Fructose, Fructose + MH-76 and Fructose + Prazosin) and subjected to biochemical and histopathological studies. Both α1-adrenolytics reduced macrovesicular steatosis and triglycerides content of liver tissue and improved its antioxidant capacity. Treatment with MH-76, contrary to prazosin, reduced leucocytes infiltration as well as decreased elevated IL-6 and leptin concentrations. Moreover, the MH-76 hepatotoxicity in hepatoma HepG2 cells was less than that of prazosin. The use of α1-adrenolytics with anti-inflammatory properties may be an interesting option for treatment of hypertension with metabolic complications. Full article
(This article belongs to the Special Issue Altered Metabolism Associated with Hypertension—a New Option for Drug Therapy?)
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17 pages, 1683 KiB  
Article
Influence of Genetic West African Ancestry on Metabolomics among Hypertensive Patients
by Mai Mehanna, Caitrin W. McDonough, Steven M. Smith, Yan Gong, John G. Gums, Arlene B. Chapman, Julie A. Johnson and Rhonda M. Cooper-DeHoff
Metabolites 2022, 12(9), 783; https://doi.org/10.3390/metabo12090783 - 24 Aug 2022
Cited by 5 | Viewed by 2038
Abstract
Patients with higher genetic West African ancestry (GWAA) have hypertension (HTN) that is more difficult to treat and have higher rates of cardiovascular diseases (CVD) and differential responses to antihypertensive drugs than those with lower GWAA. The mechanisms underlying these disparities are poorly [...] Read more.
Patients with higher genetic West African ancestry (GWAA) have hypertension (HTN) that is more difficult to treat and have higher rates of cardiovascular diseases (CVD) and differential responses to antihypertensive drugs than those with lower GWAA. The mechanisms underlying these disparities are poorly understood. Using data from 84 ancestry-informative markers in US participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, the GWAA proportion was estimated. Using multivariable linear regression, the baseline levels of 886 metabolites were compared between PEAR participants with GWAA < 45% and those with GWAA ≥ 45% to identify differential metabolites and metabolic clusters. Metabolites with a false discovery rate (FDR) < 0.2 were used to create metabolic clusters, and a cluster analysis was conducted. Differential clusters were then tested for replication in PEAR-2 participants. We identified 353 differential metabolites (FDR < 0.2) between PEAR participants with GWAA < 45% (n = 383) and those with GWAA ≥ 45% (n = 250), which were used to create 24 metabolic clusters. Of those, 13 were significantly different between groups (Bonferroni p < 0.002). Four clusters, plasmalogen and lysoplasmalogen, sphingolipid metabolism and ceramide, cofactors and vitamins, and the urea cycle, were replicated in PEAR-2 (Bonferroni p < 0.0038) and have been previously linked to HTN and CVD. Our findings may give insights into the mechanisms underlying HTN racial disparities. Full article
(This article belongs to the Special Issue Altered Metabolism Associated with Hypertension—a New Option for Drug Therapy?)
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Review

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22 pages, 1484 KiB  
Review
The Impact of Nutrient Intake and Metabolic Wastes during Pregnancy on Offspring Hypertension: Challenges and Future Opportunities
by You-Lin Tain and Chien-Ning Hsu
Metabolites 2023, 13(3), 418; https://doi.org/10.3390/metabo13030418 - 12 Mar 2023
Cited by 3 | Viewed by 2433
Abstract
Hypertension can have its origin in early life. During pregnancy, many metabolic alterations occur in the mother that have a crucial role in fetal development. In response to maternal insults, fetal programming may occur after metabolic disturbance, resulting in programmed hypertension later in [...] Read more.
Hypertension can have its origin in early life. During pregnancy, many metabolic alterations occur in the mother that have a crucial role in fetal development. In response to maternal insults, fetal programming may occur after metabolic disturbance, resulting in programmed hypertension later in life. Maternal dietary nutrients act as metabolic substrates for various metabolic processes via nutrient-sensing signals. Different nutrient-sensing pathways that detect levels of sugars, amino acids, lipids and energy are integrated during pregnancy, while disturbed nutrient-sensing signals have a role in the developmental programming of hypertension. Metabolism-modulated metabolites and nutrient-sensing signals are promising targets for new drug discovery due to their pathogenic link to hypertension programming. Hence, in this review, we pay particular attention to the maternal nutritional insults and metabolic wastes affecting fetal programming. We then discuss the role of nutrient-sensing signals linking the disturbed metabolism to hypertension programming. This review also summarizes current evidence to give directions for future studies regarding how to prevent hypertension via reprogramming strategies, such as nutritional intervention, targeting nutrient-sensing signals, and reduction of metabolic wastes. Better prevention for hypertension may be possible with the help of novel early-life interventions that target altered metabolism. Full article
(This article belongs to the Special Issue Altered Metabolism Associated with Hypertension—a New Option for Drug Therapy?)
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22 pages, 1476 KiB  
Review
Links between Metabolic Syndrome and Hypertension: The Relationship with the Current Antidiabetic Drugs
by Silviu Stanciu, Emilia Rusu, Daniela Miricescu, Ana Cristina Radu, Bianca Axinia, Ana Maria Vrabie, Ruxandra Ionescu, Mariana Jinga and Carmen Adella Sirbu
Metabolites 2023, 13(1), 87; https://doi.org/10.3390/metabo13010087 - 5 Jan 2023
Cited by 23 | Viewed by 5391
Abstract
Hypertension poses a significant burden in the general population, being responsible for increasing cardiovascular morbidity and mortality, leading to adverse outcomes. Moreover, the association of hypertension with dyslipidaemia, obesity, and insulin resistance, also known as metabolic syndrome, further increases the overall cardiovascular risk [...] Read more.
Hypertension poses a significant burden in the general population, being responsible for increasing cardiovascular morbidity and mortality, leading to adverse outcomes. Moreover, the association of hypertension with dyslipidaemia, obesity, and insulin resistance, also known as metabolic syndrome, further increases the overall cardiovascular risk of an individual. The complex pathophysiological overlap between the components of the metabolic syndrome may in part explain how novel antidiabetic drugs express pleiotropic effects. Taking into consideration that a significant proportion of patients do not achieve target blood pressure values or glucose levels, more efforts need to be undertaken to increase awareness among patients and physicians. Novel drugs, such as incretin-based therapies and renal glucose reuptake inhibitors, show promising results in decreasing cardiovascular events in patients with metabolic syndrome. The effects of sodium-glucose co-transporter-2 inhibitors are expressed at different levels, including renoprotection through glucosuria, natriuresis and decreased intraglomerular pressure, metabolic effects such as enhanced insulin sensitivity, cardiac protection through decreased myocardial oxidative stress and, to a lesser extent, decreased blood pressure values. These pleiotropic effects are also observed after treatment with glucagon-like peptide-1 receptor agonists, positively influencing the cardiovascular outcomes of patients with metabolic syndrome. The initial combination of the two classes may be the best choice in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors because of their complementary mechanisms of action. In addition, the novel mineralocorticoid receptor antagonists show significant cardio-renal benefits, as well as anti-inflammatory and anti-fibrotic effects. Overall, the key to better control of hypertension in patients with metabolic syndrome is to consider targeting multiple pathogenic mechanisms, using a combination of the different therapeutic agents, as well as drastic lifestyle changes. This article will briefly summarize the association of hypertension with metabolic syndrome, as well as take into account the influence of antidiabetic drugs on blood pressure control. Full article
(This article belongs to the Special Issue Altered Metabolism Associated with Hypertension—a New Option for Drug Therapy?)
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17 pages, 886 KiB  
Review
The Glycobiology of Pulmonary Arterial Hypertension
by Shia Vang, Phillip Cochran, Julio Sebastian Domingo, Stefanie Krick and Jarrod Wesley Barnes
Metabolites 2022, 12(4), 316; https://doi.org/10.3390/metabo12040316 - 1 Apr 2022
Cited by 8 | Viewed by 4374
Abstract
Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease of complex etiology. Cases of PAH that do not receive therapy after diagnosis have a low survival rate. Multiple reports have shown that idiopathic PAH, or IPAH, is associated with metabolic dysregulation including [...] Read more.
Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease of complex etiology. Cases of PAH that do not receive therapy after diagnosis have a low survival rate. Multiple reports have shown that idiopathic PAH, or IPAH, is associated with metabolic dysregulation including altered bioavailability of nitric oxide (NO) and dysregulated glucose metabolism. Multiple processes such as increased proliferation of pulmonary vascular cells, angiogenesis, apoptotic resistance, and vasoconstriction may be regulated by the metabolic changes demonstrated in PAH. Recent reports have underscored similarities between metabolic abnormalities in cancer and IPAH. In particular, increased glucose uptake and altered glucose utilization have been documented and have been linked to the aforementioned processes. We were the first to report a link between altered glucose metabolism and changes in glycosylation. Subsequent reports have highlighted similar findings, including a potential role for altered metabolism and aberrant glycosylation in IPAH pathogenesis. This review will detail research findings that demonstrate metabolic dysregulation in PAH with an emphasis on glycobiology. Furthermore, this report will illustrate the similarities in the pathobiology of PAH and cancer and highlight the novel findings that researchers have explored in the field. Full article
(This article belongs to the Special Issue Altered Metabolism Associated with Hypertension—a New Option for Drug Therapy?)
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