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Contraction-initiated NO-dependent lymphatic relaxation: a self-regulatory mechanism in rat thoracic duct

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Gasheva, Olga Yu., Zawieja, David C., Gashev, Anatoliy A.·2006·The Journal of Physiology
DOI 10.1113/jphysiol.2006.115212PMC PMC1995691
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Abstract

The objectives of this study were to evaluate the physiological importance of the flow and shear generated by phasic contractions of lymphatic vessels and the mechanisms responsible for the influences of such shear on lymphatic pumping. Lymphatic segments of the rat thoracic duct were isolated, cannulated and pressurized. The diastolic diameters were measured in phasically non‐active segments. The diastolic and systolic diameters, half‐relaxation time (HRT), contraction frequency, ejection fraction and fractional pump flow were determined in phasically active segments. Since imposed flow was excluded, flow and shear occurred only as a result of the intrinsic contractions in phasically active segments whereas in phasically non‐active segments contraction‐generated flow and shear were absent. The influences of incrementally increased transmural pressure (from 1 to 5 cmH 2 O) were examined in control conditions and after NO synthase blockade ( l ‐NAME 10 −4 m ) or cyclooxygenase blockade (indomethacin 10 −5 m ). The spontaneous phasic contractions produced a flow‐dependent diastolic relaxation. This reduction of the lymphatic tone is a regulatory mechanism that maintains pumping in thoracic duct in an energy‐saving/efficient mode: it improves diastolic filling (enhanced lusitropy – lowering HRT), makes lymphatic contractions stronger (enhanced inotropy – higher contraction amplitude) and propels more fluid forward during each contraction (elevated ejection fraction) while decreasing contraction frequency (reduced chronotropy). The findings also demonstrated that the NO pathway, not the cyclooxygenase pathway is responsible for this reduction of lymphatic tone and is the prevailing pathway responsible for the self‐regulatory adjustment of thoracic duct pumping to changes in lymph flow pattern.

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  • At low concentrations associated with pulsatile flow, nitric oxide enhances the speed of diastolic relaxation, allowing more time for filling and thereby increasing contraction amplitude in the subsequent contraction cycle.

    “At low concentrations associated with pulsatile flow, NO enhances the speed of diastolic relaxation, allowing more time for filling and thereby increasing the contraction amplitude in the subsequent contraction cycle (72).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [72]

    The Results report that blocking NO synthesis lengthened half-relaxation time and reduced contraction amplitude in phasically contracting rat thoracic duct segments; they also say contraction-generated NO eases diastolic filling. The Discussion contrasts NO released during phasic contractions with larger releases under increased inflow, but says NO concentrations were not measured. The proposed link from faster relaxation to greater amplitude in the subsequent cycle is plausible, but is not directly established in these passages. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Gasheva, O. Y., Zawieja, D. C., & Gashev, A. A.
Affiliations
Texas A&M Health Science Center (US)
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2006-09-06
Volume
575
Issue
3
Pages
821-832
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.2006.115212
PMC
PMC1995691
OpenAlex
W2101192212
Cited by
181
References
0
Citations by year
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FWCI
4.17
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL070308, HL070308, R01HL075199, HL075199)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Keywords
thoracic duct, lymphatic vessels, lymphatic contraction, shear stress, nitric oxide, lymphatic pumping, lymph flow, nitric oxide synthase, cyclooxygenase, indomethacin, L-NAME, contraction frequency, ejection fraction, self-regulation
MeSH terms
Animals, Enzyme Inhibitors, Homeostasis, Lymphatic System, Male, Muscle Contraction, Muscle Relaxation, Muscle, Smooth, Nitric Oxide, Pressure, Rheology, Stress, Mechanical, Thoracic Duct, Rats, Sprague-Dawley, Nitric Oxide Synthase, NG-Nitroarginine Methyl Ester, Rats, In Vitro Techniques

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