Effects of hypoxia in porcine pulmonary arterial myocytes: roles of K(V) channel and endothelin-1.
Effects of acute hypoxia on intracellular Ca(2+) concentration ([Ca(2+)](i)) and cell length were recorded simultaneously in proximal and distal pulmonary (PASMCs) and femoral (FASMCs) arterial smooth muscle cells. Reducing PO(2) from normoxia to severe hypoxia (PO(2) < 10 mmHg) caused small but significant decreases in length and a reversible increase in [Ca(2+)](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(+) (K(V)) channel with 4-aminopyridine produced a greater increase in [Ca(2+)](i) in distal than in proximal PASMCs. In distal PASMCs, severe hypoxia caused a slight inhibition of K(V) 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 [Ca(2+)](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 K(V) channels and were greatly enhanced via synergistic interactions with the endothelium-derived factor endothelin-1.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21224, USA. jsks@welchlink.welch.jhu.edu
J S
JS
Sham
B R
BR
Crenshaw
L H
LH
Deng
L A
LA
Shimoda
J T
JT
Sylvester
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D007476:Ionophores; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D010656:Phenylephrine; D012701:Serotonin; D000001:Calcimycin; D011189:Potassium Chloride; D015761:4-Aminopyridine; D002118:Calcium