Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrapulmonary veins (PVs) contribute to pulmonary vascular resistance, but the mechanisms controlling PV tone are poorly understood. Although smooth muscle cell (SMC) K(+) channels regulate tone in most vascular beds, their role in PV tone is unknown. We show that voltage-gated (K(V)) and inward rectifier (K(ir)) K(+) channels control resting PV tone in the rat. PVs have a coaxial structure, with layers of cardiomyocytes (CMs) arrayed externally around a subendothelial layer of typical SMCs, thus forming spinchterlike structures. PVCMs have both an inward current, inhibited by low-dose Ba(2+), and an outward current, inhibited by 4-aminopyridine. In contrast, PVSMCs lack inward currents, and their outward current is inhibited by tetraethylammonium (5 mM) and 4-aminopyridine. Several K(V), K(ir), and large-conductance Ca(2+)-sensitive K(+) channels are present in PVs. Immunohistochemistry showed that K(ir) channels are present in PVCMs and PV endothelial cells but not in PVSMCs. We conclude that K(+) channels are present and functionally important in rat PVs. PVCMs form sphincters rich in K(ir) channels, which may modulate venous return both physiologically and in disease states including pulmonary edema.
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PMID:Potassium channels regulate tone in rat pulmonary veins. 1135 Jul 92

This review describes the ionic heterogeneity manifest in the pulmonary circulation, particularly as it pertains to hypoxic pulmonary vasoconstriction (HPV) and pulmonary arterial hypertension (PAH). Heterogeneity in potassium (K(+)) channels, key regulators of vascular tone, cell proliferation, and apoptosis rates, contribute to the diverse response of vascular segments to hypoxia and to the localization of pathological changes in PAH. Pulmonary artery (PA) and pulmonary vein (PV) smooth muscle cells (SMC) express several K(+) channel families, including calcium-sensitive (KCa), voltage-gated (K(v)), inward rectifier (Kir), and 2-pore channels. Diversity is created by heterogeneous occurrence of alternatively spliced, mRNA species, assembly of heterotetrameric channels from diverse alpha-subunits, and association of channels with regulatory beta-subunits. Local heterogeneity in transcription factor activity may underlie differences in channel expression. Enrichment of resistance PASMCs with O(2)-sensitive K(+) channels, such as K(v)1.5, partially explains the greater HPV in resistance versus conduit PAs. In addition, resistance PAs are unique in having mitochondria which dynamically alter production of reactive O(2) species (ROS) in proportion to PO(2), thereby regulating K(+) channel activity and controlling expression through transcription factors, such as HIF-1alpha. In intraparenchymal PVs, a coaxial layer of cardiomyocytes encompasses a media of typical vascular SMCs. PV cardiomyocytes have rhythmic contraction and their Kir-enriched channels may be relevant to genesis of atrial arrhythmias and pulmonary edema. K(v) channel expression is decreased in PAH, leading to elevations of cytosolic K(+) and Ca(2+) that impair apoptosis and increase proliferation. Understanding ionic diversity may allow development of therapies that locally increase K(+) channel current and expression to treat PHT.
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PMID:Potassium channel diversity in the pulmonary arteries and pulmonary veins: implications for regulation of the pulmonary vasculature in health and during pulmonary hypertension. 1758 56