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Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21224
Effects of acute
hypoxia on intracellular Ca2+ concentration
([Ca2+]i) and cell length were recorded
simultaneously in proximal and distal pulmonary (PASMCs) and femoral
(FASMCs) arterial smooth muscle cells. Reducing
PO2 from normoxia to severe hypoxia
(PO2 < 10 mmHg) caused small but
significant decreases in length and a reversible increase in
[Ca2+]i in distal PASMCs and a small decrease
in length in proximal PASMCs but had no effect in FASMCs, even though
all three cell types contracted significantly to vasoactive agonists.
Inhibition of voltage-dependent K+ (KV) channel
with 4-aminopyridine produced a greater increase in
[Ca2+]i in distal than in proximal PASMCs. In
distal PASMCs, severe hypoxia caused a slight inhibition of
KV currents; however, it elicited further contraction in
the presence of 4-aminopyridine. Endothelin-1 (10
10 M),
which itself did not alter cell length or
[Ca2+]i, significantly potentiated the
hypoxic contraction. These results suggest that hypoxia only has small
direct effects on porcine PASMCs. These effects cannot be fully
explained by inhibition of KV channels and were greatly
enhanced via synergistic interactions with the endothelium-derived
factor endothelin-1.
vasoconstriction; calcium; voltage-dependent potassium channel; pulmonary arterial smooth muscle cell
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