High K+-induced membrane depolarization attenuates endothelium- dependent pulmonary vasodilation

Jan E. Seiden, Oleksandr Platoshyn, Alan E. Bakst, Sharon S. Mcdaniel, Jason Yuan

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Impairment of endothelium-dependent pulmonary vasodilation has been implicated in the development of pulmonary hypertension. Pulmonary vascular smooth muscle cells and endothelial cells communicate electrically through gap junctions; thus, membrane depolarization in smooth muscle cells would depolarize endothelial cells. In this study, we examined the effect of prolonged membrane depolarization induced by high K+ on the endothelium- dependent pulmonary vasodilation. Isometric tension was measured in isolated pulmonary arteries (PA) from Sprague-Dawley rats, and membrane potential was measured in single PA smooth muscle cells. Increase in extracellular K+ concentration from 4.7 to 25 mM significantly depolarized PA smooth muscle cells. The 25 mM K+-mediated depolarization was characterized by an initial transient depolarization (5-15 s) followed by a sustained depolarization that could last for up to 3 h. In endothelium-intact PA rings, ACh (2 μM), levcromakalim (10 μM), and nitroprusside (10 μM) reversibly inhibited the 25 mM K+mediated contraction. Functional removal of endothelium abolished the ACh-mediated relaxation but had no effect on the levcromakalim- or the nitroprusside-mediated pulmonary vasodilation. Prolonged (~3 h) membrane depolarization by 25 mM K+ significantly inhibited the ACh-mediated PA relaxation (-55 ± 4 vs. -29 ± 2%, P < 0.001), negligibly affected the levcromakalim-mediated pulmonary vasodilation (-92 ± 4 vs. -95 ± 5%), and slightly but significantly increased the nitroprusside-mediated PA relaxation (- 80 ± 2 vs. 90 ± 3%, P < 0.05). These data indicate that membrane depolarization by prolonged exposure to high K+ concentration selectively inhibited endothelium-dependent pulmonary vasodilation, suggesting that membrane depolarization plays a role in the impairment of pulmonary endothelial function in pulmonary hypertension.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number2 22-2
StatePublished - Feb 2000
Externally publishedYes

Fingerprint

Vasodilation
Endothelium
Pulmonary Artery
Lung
Cromakalim
Membranes
Smooth Muscle Myocytes
Nitroprusside
Pulmonary Hypertension
Endothelial Cells
Gap Junctions
Vascular Smooth Muscle
Membrane Potentials
Sprague Dawley Rats

Keywords

  • Membrane potential
  • Pulmonary circulation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

High K+-induced membrane depolarization attenuates endothelium- dependent pulmonary vasodilation. / Seiden, Jan E.; Platoshyn, Oleksandr; Bakst, Alan E.; Mcdaniel, Sharon S.; Yuan, Jason.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 278, No. 2 22-2, 02.2000.

Research output: Contribution to journalArticle

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