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Abstract

BACKGROUND:

Hypertension increases the risk of lymphedema in patients with comorbidities, but whether hypertension directly compromises lymph vessel (LV) function and lymph flow is unclear. We compared the contractions of mesenteric LVs ex vivo and lymph flow in vivo between normotensive and Ang II (angiotensin II)-induced hypertensive rats and explored the ionic basis of contractile patterns. Key studies were recapitulated in spontaneously hypertensive rats and control Wistar-Kyoto rats.

METHODS:

Video microscopy continuously recorded the diameters of cannulated rat mesenteric LVs, and high-speed optical imaging estimated mesenteric lymph flow in vivo. Jess capillary Western electrophoresis evaluated expression levels of ion channel proteins.

RESULTS:

Isolated LVs from Ang II-induced hypertensive rats exhibited dysrhythmic contractions, whereas LVs from both Ang II-induced hypertensive rats and spontaneously hypertensive rats exhibited reduced diastolic diameters and cross-sectional flow. Mesenteric lymph flow in vivo was 2.9-fold lower in Ang II-induced hypertensive rats compared with normotensive rats. Surprisingly, the LVs from Ang II-induced hypertensive rats expressed fewer intact L-type Ca2+ channel pore proteins and more modulatory cleaved C-terminal fragments. However, pharmacological block of voltage-gated K+ channels but not other K+ channel types in control LVs established the pattern of contractile dysfunction observed in hypertension. Jess capillary Western electrophoresis analysis confirmed a loss of Shaker-type KV1.2 channels in LVs from hypertensive rats.

CONCLUSIONS:

We provide initial evidence of lymphatic contractile dysfunction and compromised lymph flow in hypertensive rats, which may be caused by a loss of KV1.2 channels in the lymphatic muscle cells.

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Published In

Go to Hypertension
Go to Hypertension
Hypertension
PubMed: 39502071

History

Received: 22 April 2024
Accepted: 16 October 2024
Published online: 6 November 2024

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Keywords

  1. humans
  2. hypertension
  3. lymphedema
  4. muscle cells
  5. rats

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Authors

Affiliations

Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock (S.P., A.K.B., A.J.S.)
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock (S.P., A.K.B., A.J.S.)
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock (D.S.H., S.M., S.W.R., N.J.R., A.J.S.)
Department of Biostatistics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock (R.D.L.)
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock (D.S.H., S.M., S.W.R., N.J.R., A.J.S.)
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock (D.S.H., S.M., S.W.R., N.J.R., A.J.S.)
Now with Department of Biomedical Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA (S.W.R.).
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock (D.S.H., S.M., S.W.R., N.J.R., A.J.S.)
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock (S.P., A.K.B., A.J.S.)
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock (D.S.H., S.M., S.W.R., N.J.R., A.J.S.)

Notes

For Sources of Funding and Disclosures, see page XXX.
Supplemental Material is available at Supplemental Material.
Correspondence to: Amanda J. Stolarz, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, 4301 W. Markham St, #622, Little Rock, AR 72205-7199. Email [email protected]

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Rhythmic Contractions of Lymph Vessels and Lymph Flow Are Disrupted in Hypertensive Rats
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