ArticleThe Journal of physiology2013
Genetic removal of basal nitric oxide enhances contractile activity in isolated murine collecting lymphatic vessels.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 119 citations in OpenAlex.
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- Roles of G-protein coupled receptors and mechanosensitive ion channels in pressure-induced chronotropy of lymphatic vessels.bioRxiv : the preprint server for biology · 2025Article
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- Control of lymphatic pacemaking and pumping by mechanobiological signals.The Journal of physiology · 2025Article
- Chronic metabolic stress impairs lymphatic contractility via activation of KATP channels in a mouse model of Type-2 diabetes.Frontiers in physiology · 2025Article
- Overview of Lymphatic Muscle Cells in Development, Physiology, and Disease.Microcirculation (New York, N.Y. : 1994) · 2024Review
- Acute Metabolic Stress Induces Lymphatic Dysfunction Through KATP Channel Activation.Function (Oxford, England) · 2024Article
- Molecular pathophysiology of secondary lymphedema.Frontiers in cell and developmental biology · 2024Review
- Targeting lymphatic function in cardiovascular-kidney-metabolic syndrome: preclinical methods to analyze lymphatic function and therapeutic opportunities.Frontiers in cardiovascular medicine · 2024Review
- Topical captopril: a promising treatment for secondary lymphedema.Translational research : the journal of laboratory and clinical medicine · 2023Article
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- KAmerican journal of physiology. Cell physiology · 2022Review
- Lymphatic Vascular Permeability.Cold Spring Harbor perspectives in medicine · 2022Review
- Persistent popliteal lymphatic muscle cell coverage defects despite amelioration of arthritis and recovery of popliteal lymphatic vessel function in TNF-Tg mice following anti-TNF therapy.Scientific reports · 2022Article
- Current Understanding of Pathological Mechanisms of Lymphedema.Advances in wound care · 2022Review
- Effect of Human Synovial Fluid From Osteoarthritis Patients and Healthy Individuals on Lymphatic Contractile Activity.Journal of biomechanical engineering · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The role of nitric oxide (NO) in regulating lymphatic contractile function and, consequently, lymph flow has been the subject of intense study. Despite this, the precise effects of NO on lymphatic contractile activity remain unclear. Recent hypotheses posit that basal levels of endogenous NO increase lymphatic contraction strength as a consequence of lowering frequency (i.e. positive lusitropy), whereas higher agonist-evoked concentrations of NO exert purely inhibitory effects on contractile function. We tested both hypotheses directly by isolating and cannulating collecting lymphatic vessels from genetically modified mice for ex vivo study. The effects of basal NO and agonist-evoked NO were evaluated, respectively, by exposing wild-type (WT), endothelial NO synthase (eNOS)(-/-) and inducible NO synthase (iNOS)(-/-) lymphatic vessels to controlled pressure steps followed by ACh doses. To compare with pharmacological inhibition of eNOS, we repeated both tests in the presence of l-NAME. Surprisingly, genetic removal of basal NO enhanced contraction amplitude significantly without increasing contraction frequency. Higher levels of NO production stimulated by ACh evoked dilation, decreased tone, slowed contraction frequency and reduced fractional pump flow. We conclude that basal NO specifically depresses contraction amplitude, and that greater NO production then inhibits all other aspects of contractile function. Further, this work demonstrates definitively that mouse collecting lymphatic vessels exhibit autonomous, large-amplitude contractions that respond to pressure similarly to collecting lymphatics of other mammalian species. At least in the peripheral lymphatic vasculature, NO production depresses contractile function, which influences lymph flow needed for fluid regulation, humoral immunity and cancer metastasis.
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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.