ArticleCardiovascular research2021
Failure to vasodilate in response to salt loading blunts renal blood flow and causes salt-sensitive hypertension.
Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Effects of excess sodium consumption on arterial function in C57BL/6 mice.American journal of physiology. Heart and circulatory physiology · 2024Pooled it
- Dietary Sodium-Regulated Plasma SVEP1 and Inverse Salt Sensitivity.Hypertension (Dallas, Tex. : 1979) · 2026Trial
- Neuroendocrine regulatory effects of sex hormones on salt sensitivity of blood pressure.Nature reviews. Cardiology · 2025Article
- SVEP1 Upregulation Is a Prominent Molecular Response to Dietary Sodium Loading and Correlates with Inverse Salt Sensitivity.medRxiv : the preprint server for health sciences · 2025Article
- Global, regional, and national burden of hypertension-induced cardiorenal disease, 1990-2021 and projections to 2050: a systematic analysis for the global burden of disease study 2021.BMC public health · 2025Article
- Decoding the anti-hypertensive mechanism of α-mangostin based on network pharmacology, molecular docking and experimental validation.Molecular medicine (Cambridge, Mass.) · 2024Article
- The Pathogenesis and Impact of Arterial Stiffening in Hypertension: The 2023 John H. Laragh Research Award.American journal of hypertension · 2024Article
- Sex differences in blood pressure regulation and hypertension: renal, hemodynamic, and hormonal mechanisms.Physiological reviews · 2024Review
- Paradigm Shift in Hyperglycemic Glomerular Hyperfiltration: Blunted Tubuloglomerular Feedback or Preglomerular Vasodilation?Hypertension (Dallas, Tex. : 1979) · 2023Article
- Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension.Function (Oxford, England) · 2023Article
- Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway.International journal of molecular sciences · 2022Article
- RhoBTB1 reverses established arterial stiffness in angiotensin II-induced hypertension by promoting actin depolymerization.JCI insight · 2022Article
- The impact of excessive salt intake on human health.Nature reviews. Nephrology · 2022Review
- Galectin-9 deficiency exacerbates lipopolysaccharide-induced hypothermia and kidney injury.Clinical and experimental nephrology · 2022Article
- Effects of sea salt intake on metabolites, steroid hormones, and gut microbiota in rats.PloS one · 2022Article
- Endothelial Cullin3 Mutation Impairs Nitric Oxide-Mediated Vasodilation and Promotes Salt-Induced Hypertension.Function (Oxford, England) · 2022Article
- Role of the Peroxisome Proliferator Activated Receptors in Hypertension.Circulation research · 2021Review
- Mechanism of herbal medicine on hypertensive nephropathy (Review).Molecular medicine reports · 2021Review
- EP3 (E-Prostanoid 3) Receptor Mediates Impaired Vasodilation in a Mouse Model of Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2021Article
- The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases.International journal of molecular sciences · 2021Review
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13 authors at 2 institutions in 1 country.
Funding
Abstract
aimsSalt-sensitive (SS) hypertension is accompanied by impaired vasodilation in the systemic and renal circulation. However, the causal relationship between vascular dysfunction and salt-induced hypertension remains controversial. We sought to determine whether primary vascular dysfunction, characterized by a failure to vasodilate during salt loading, plays a causal role in the pathogenesis of SS hypertension. METHODS AND
resultsMice selectively expressing a peroxisome proliferator-activated receptor γ dominant-negative mutation in vascular smooth muscle (S-P467L) exhibited progressive SS hypertension during a 4 week high salt diet (HSD). This was associated with severely impaired vasodilation in systemic and renal vessels. Salt-induced impairment of vasodilation occurred as early as 3 days after HSD, which preceded the onset of SS hypertension. Notably, the overt salt-induced hypertension in S-P467L mice was not driven by higher cardiac output, implying elevations in peripheral vascular resistance. In keeping with this, HSD-fed S-P467L mice exhibited decreased smooth muscle responsiveness to nitric oxide (NO) in systemic vessels. HSD-fed S-P467L mice also exhibited elevated albuminuria and a blunted increase in urinary NO metabolites which was associated with blunted renal blood flow and increased sodium retention mediated by a lack of HSD-induced suppression of NKCC2. Blocking NKCC2 function prevented the salt-induced increase in blood pressure in S-P467L mice.
conclusionWe conclude that failure to vasodilate in response to salt loading causes SS hypertension by restricting renal perfusion and reducing renal NO through a mechanism involving NKCC2 in a mouse model of vascular peroxisome proliferator-activated receptor γ impairment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.