Effects of hypoxia in porcine pulmonary arterial myocytes: roles of KVchannel and endothelin-1

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Abstract
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 Po2from normoxia to severe hypoxia (Po2< 10 mmHg) caused small but significant decreases in length and a reversible increase in [Ca2+]iin 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+]iin distal than in proximal PASMCs. In distal PASMCs, severe hypoxia caused a slight inhibition of KVcurrents; however, it elicited further contraction in the presence of 4-aminopyridine. Endothelin-1 (10−10M), 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 KVchannels and were greatly enhanced via synergistic interactions with the endothelium-derived factor endothelin-1.