ArticleJournal of the American Society of Nephrology : JASN2020
Sympathetic Overactivity in CKD Disrupts Buffering of Neurotransmission by Endothelium-Derived Hyperpolarizing Factor and Enhances Vasoconstriction.
Article in Journal of the American Society of Nephrology : JASN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- The Interaction of Central Nervous System and Acute Kidney Injury: Pathophysiology and Clinical Perspectives.Frontiers in physiology · 2022Pooled it
- The Lung-Kidney Axis: A Coordinated Regulation of Oxygen Sensing and Erythropoiesis.Biomedicines · 2026Review
- Unveiling the molecular toxicity of plasticizers derived from microplastics (DMP and DEP) in diabetic kidney disease: integrative insights from network toxicology and multi-omics analysis.Frontiers in immunology · 2026Article
- Autonomic-vascular dysregulation in CKD-associated hypertension: a narrative review with evidence hierarchy.Frontiers in neuroscience · 2026Review
- Stress Pathways in Chronic Kidney Disease: Linking Cortisol, Oxidative Stress, and Inflammation.Antioxidants (Basel, Switzerland) · 2025Review
- Vasomotor responses are similar between outbred UM-HET3 and inbred C57BL/6J male and female mouse mesenteric resistance arteries.Frontiers in physiology · 2025Article
- Mechanisms of Congestion in Acute Decompensated Heart Failure.Cardiorenal medicine · 2025Review
- Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction.iScience · 2023Article
- Physiological Mechanisms of Hypertension and Cardiovascular Disease in End-Stage Kidney Disease.Current hypertension reports · 2022Review
- Kidney and epigenetic mechanisms of salt-sensitive hypertension.Nature reviews. Nephrology · 2021Review
- Pathophysiology of Hypertension: The Mosaic Theory and Beyond.Circulation research · 2021Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypertension commonly complicates CKD. Vascular smooth muscle cells (VSMCs) of resistance arteries receive signals from the sympathetic nervous system that induce an endothelial cell (EC)-dependent anticontractile response that moderates vasoconstriction. However, the specific role of this pathway in the enhanced vasoconstriction in CKD is unknown.
methodsA mouse model of CKD hypertension generated with 5/6-nephrectomy (5/6Nx) was used to investigate the hypothesis that an impaired anticontractile mechanism enhances sympathetic vasoconstriction.
resultsBy 4 weeks, 5/6Nx mice (versus sham) had augmented increases in mesenteric vascular resistance and mean arterial pressure with carotid artery occlusion, accompanied by decreased connexin 43 (Cx43) expression at myoendothelial junctions (MEJs), impaired gap junction function, decreased EC-dependent hyperpolarization (EDH), and enhanced contractions. Exposure of VSMCs to NE for 24 hours in a vascular cell coculture decreased MEJ Cx43 expression and MEJ gap junction function. These changes preceded vascular structural changes evident only at week 8. Inhibition of central sympathetic outflow or transfection of Cx43 normalized neurovascular transmission and vasoconstriction in 5/6Nx mice.
conclusions5/6Nx mice have enhanced neurovascular transmission and vasoconstriction from an impaired EDH anticontractile component before vascular structural changes. These neurovascular changes depend on an enhanced sympathetic discharge that impairs the expression of Cx43 in gap junctions at MEJs, thereby interrupting EDH responses that normally moderate vascular tone. Dysregulation of neurovascular transmission may contribute to the development of hypertension in CKD.
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