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Sympathetic Nerves and Cardiovascular Diseases 2.0
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Sympathetic Nerves and Cardiovascular Diseases 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 May 2024 | Viewed by 10452

Special Issue Editors

Dr. Yutang Wang

E-Mail Website
Guest Editor
Discipline of Life Science, Institute of Innovation, Science and Sustainability, Federation University Australia, Ballarat, VIC 3350, Australia
Interests: cardiovascular disease; hypertension; diabetes; atherosclerosis; abdominal aortic aneurysm; renal denervation; dyslipidemia; hyperuricemia
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Kate Denton

E-Mail Website
Guest Editor
Department of Physiology, Monash University, Melbourne, VIC 3800, Australia
Interests: cardiovascular disease; kidney disease; renin-angiotensin system; renal sympathetic nerves; hypertension; pregnancy

Special Issue Information

Dear Colleagues, 

This Special Issue is a continuation of our previous Special Issue “Sympathetic Nerves and Cardiovascular Diseases”.

Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels, including heart attack and stroke. According to the World Health Organization, cardiovascular diseases (CVDs) are the leading causes of death globally. An estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. The common risk factors for CVDs include hypertension, diabetes, dyslipidemia, and obesity, among others. It has been shown that sympathetic nerve activity is often increased under these conditions, and the inhibition of sympathetic nerve activity (e.g., via renal denervation) has been shown to decrease blood pressure and improve glycemic control. This Special Issue of IJMS will cover the latest developments in the effect of sympathetic nerve activity on CVDs. It will explore the molecular mechanisms underlying the contribution of sympathetic nerve activity to the development of CVDs. Articles focusing on the effect of sympathetic nerve activity on heart failure, arrhythmia, stroke, atherosclerosis, hypertension, diabetes, dyslipidemia, obesity, and renal disease are of particular interest.

Dr. Yutang Wang
Prof. Dr. Kate Denton
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • sympathetic nerve activity
  • renal denervation
  • heart disease
  • stroke
  • atherosclerosis
  • hypertension
  • vascular remodeling
  • diabetes
  • metabolic syndrome
  • kidney disease

Published Papers (4 papers)

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Research

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20 pages, 1638 KiB  
Article
Effect of Low-Frequency Renal Nerve Stimulation on Renal Glucose Release during Normoglycemia and a Hypoglycemic Clamp in Pigs
by Marius Nistor, Martin Schmidt, Carsten Klingner, Caroline Klingner, Georg Matziolis, Sascha Shayganfar and René Schiffner
Int. J. Mol. Sci. 2024, 25(4), 2041; https://doi.org/10.3390/ijms25042041 - 07 Feb 2024
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Abstract
Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a [...] Read more.
Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a pulse generator (2–5 Hz) during normoglycemia (60 min) and insulin-induced hypoglycemia ≤3.5 mmol/L (75 min) in seven pigs. The jugular vein, carotid artery, renal artery and vein, and both ureters were catheterized for measurement purposes, blood pressure management, and drug and fluid infusions. Para-aminohippurate (PAH) and inulin infusions were used to determine side-dependent renal plasma flow (SRP) and glomerular filtration rate (GFR). In a linear mixed model, LFS caused no change in SRP but decreased sodium excretion (p < 0.0001), as well as decreasing GFR during hypoglycemia (p = 0.0176). In a linear mixed model, only hypoglycemic conditions exerted significant effects on SGN (p = 0.001), whereas LFS did not. In a Wilcoxon signed rank exact test, LFS significantly increased SGN (p = 0.03125) and decreased sodium excretion (p = 0.0017) and urinary flow rate (p = 0.0129) when only considering the first instance LFS followed a preceding period of non-stimulation during normoglycemia. To conclude, this study represents, to our knowledge, the first description of an induction of renal gluconeogenesis by LFS. Full article
(This article belongs to the Special Issue Sympathetic Nerves and Cardiovascular Diseases 2.0)
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17 pages, 1212 KiB  
Article
Renal Glucose Release after Unilateral Renal Denervation during a Hypoglycemic Clamp in Pigs with an Altered Hypothalamic Pituitary Adrenal Axis after Late-Gestational Dexamethasone Injection
by Marius Nistor, Martin Schmidt, Carsten Klingner, Caroline Klingner, Matthias Schwab, Sabine Juliane Bischoff, Georg Matziolis, Guadalupe Leticia Rodríguez-González and René Schiffner
Int. J. Mol. Sci. 2023, 24(16), 12738; https://doi.org/10.3390/ijms241612738 - 13 Aug 2023
Cited by 1 | Viewed by 1016
Abstract
Previously, we demonstrated in pigs that renal denervation halves glucose release during hypoglycaemia and that a prenatal dexamethasone injection caused increased ACTH and cortisol concentrations as markers of a heightened hypothalamic pituitary adrenal axis (HPAA) during hypoglycaemia. In this study, we investigated the [...] Read more.
Previously, we demonstrated in pigs that renal denervation halves glucose release during hypoglycaemia and that a prenatal dexamethasone injection caused increased ACTH and cortisol concentrations as markers of a heightened hypothalamic pituitary adrenal axis (HPAA) during hypoglycaemia. In this study, we investigated the influence of an altered HPAA on renal glucose release during hypoglycaemia. Pigs whose mothers had received two late-gestational dexamethasone injections were subjected to a 75 min hyperinsulinaemic–hypoglycaemic clamp (<3 mmol/L) after unilateral surgical denervation. Para-aminohippurate (PAH) clearance, inulin, sodium excretion and arterio–venous blood glucose difference were measured every fifteen minutes. The statistical analysis was performed with a Wilcoxon signed-rank test. PAH, inulin, the calculated glomerular filtration rate and plasma flow did not change through renal denervation. Urinary sodium excretion increased significantly (p = 0.019). Side-dependent renal net glucose release (SGN) decreased by 25 ± 23% (p = 0.004). At 25 percent, the SGN decrease was only half of that observed in non-HPAA-altered animals in our prior investigation. The current findings may suggest that specimens with an elevated HPAA undergo long-term adaptations to maintain glucose homeostasis. Nonetheless, the decrease in SGN warrants further investigations and potentially caution in performing renal denervation in certain patient groups, such as diabetics at risk of hypoglycaemia. Full article
(This article belongs to the Special Issue Sympathetic Nerves and Cardiovascular Diseases 2.0)
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Review

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19 pages, 3353 KiB  
Review
Sympathetic Nervous System and Atherosclerosis
by Yutang Wang, Jack Anesi, Michelle C. Maier, Mark A. Myers, Ernesto Oqueli, Christopher G. Sobey, Grant R. Drummond and Kate M. Denton
Int. J. Mol. Sci. 2023, 24(17), 13132; https://doi.org/10.3390/ijms241713132 - 23 Aug 2023
Cited by 2 | Viewed by 2683
Abstract
Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional [...] Read more.
Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis. In this article, we reviewed the sympathetic innervation in the vasculature, norepinephrine synthesis and metabolism, sympathetic activity measurement, and common signaling pathways of sympathetic activation. The focus of this paper was to review the effectiveness of pharmacological antagonists or agonists of adrenoceptors (α1, α2, β1, β2, and β3) and renal denervation on atherosclerosis. All five types of adrenoceptors are present in arterial blood vessels. α1 blockers inhibit atherosclerosis but increase the risk of heart failure while α2 agonism may protect against atherosclerosis and newer generations of β blockers and β3 agonists are promising therapies against atherosclerosis; however, new randomized controlled trials are warranted to investigate the effectiveness of these therapies in atherosclerosis inhibition and cardiovascular risk reduction in the future. The role of renal denervation in atherosclerosis inhibition in humans is yet to be established. Full article
(This article belongs to the Special Issue Sympathetic Nerves and Cardiovascular Diseases 2.0)
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14 pages, 1140 KiB  
Review
Sex Differences in Neurovascular Control: Implications for Obstructive Sleep Apnea
by Joshua M. Bock, Ian M. Greenlund, Virend K. Somers and Sarah E. Baker
Int. J. Mol. Sci. 2023, 24(17), 13094; https://doi.org/10.3390/ijms241713094 - 23 Aug 2023
Viewed by 1269
Abstract
Patients with obstructive sleep apnea (OSA) have a heightened risk of developing cardiovascular diseases, namely hypertension. While seminal evidence indicates a causal role for sympathetic nerve activity in the hypertensive phenotype commonly observed in patients with OSA, no studies have investigated potential sex [...] Read more.
Patients with obstructive sleep apnea (OSA) have a heightened risk of developing cardiovascular diseases, namely hypertension. While seminal evidence indicates a causal role for sympathetic nerve activity in the hypertensive phenotype commonly observed in patients with OSA, no studies have investigated potential sex differences in the sympathetic regulation of blood pressure in this population. Supporting this exploration are large-scale observational data, as well as controlled interventional studies in healthy adults, indicating that sleep disruption increases blood pressure to a greater extent in females relative to males. Furthermore, females with severe OSA demonstrate a more pronounced hypoxic burden (i.e., disease severity) during rapid eye movement sleep when sympathetic nerve activity is greatest. These findings would suggest that females are at greater risk for the hemodynamic consequences of OSA and related sleep disruption. Accordingly, the purpose of this review is three-fold: (1) to review the literature linking sympathetic nerve activity to hypertension in OSA, (2) to highlight recent experimental data supporting the hypothesis of sex differences in the regulation of sympathetic nerve activity in OSA, and (3) to discuss the potential sex differences in peripheral adrenergic signaling that may contribute to, or offset, cardiovascular risk in patients with OSA. Full article
(This article belongs to the Special Issue Sympathetic Nerves and Cardiovascular Diseases 2.0)
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