title: High K(+)-induced membrane depolarization attenuates endothelium-dependent pulmonary vasodilation.
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 microM), levcromakalim (10 microM), and nitroprusside (10 microM) 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 ( approximately 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.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Seiden
authors.forename: O
authors.initials: O
authors.lastname: Platoshyn
authors.forename: A E
authors.initials: AE
authors.lastname: Bakst
authors.forename: S S
authors.initials: SS
authors.lastname: McDaniel
authors.forename: J X
authors.initials: JX
authors.lastname: Yuan
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008566:Membranes / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D000109:Acetylcholine; D011188:Potassium