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 language | English (US) |
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Pages (from-to) | L261-L267 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 278 |
Issue number | 2 22-2 |
DOIs | |
State | Published - Feb 2000 |
Externally published | Yes |
Keywords
- Membrane potential
- Pulmonary circulation
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology