Differential effects of hypoxia and 4-aminopyridine (4-AP) in intracellular [Ca2+] and cell-length in porcine distal and proximal pulmonary and femoral arterial smooth muscle cells (ASMCs)

James Sham, B. R. Crenshaw, J. T. Sylvester

Research output: Contribution to journalArticle

Abstract

Acute hypoxia is thought to cause vasoconstriction in pulmonary arteries, but relaxation in systemic arteries. It has been proposed that inhibition of 4-AP sensitive (delayed rectifier) K+ channels in pulmonary ASMCs mediate hypoxic pulmonary vasoconstriction. We tested this hypothesis by examining (1) whether there was a correlation between the hypoxia and 4-AP induced responses in porcine pulmonary and femoral ASMCs and (2) whether the hypoxic responses was altered by inhibiting delayed rectifier K+ channels. ASMCs were isolated enzymatically from proximal (> 1 cm o.d.) and distal (0.3-0.8 mm o.d.) intralobar pulmonary arteries and femoral arteries. [Ca2+], and cell-length of single freshly isolated ASMC were monitored simultaneously using Indo-1 AM and video-microscopy. A decrease in pO2 from 110 mmHg to <10 mmHg had no effect in femoral and poximal pulmonary ASMCs. but caused small but significant increases in [Ca2+] and decreases in cell-length in distal PASMCs. In contrast, 4-AP (10 mM) increased [Ca2+]i and decreased cell-length in distal pulmonary and femoral ASMCs, but had no significant effect in proximal pulmonary ASMCs. All three types of myocytes responded to KCl (100 mM) to a similar extent. In the presence of 10 mM 4-AP, hypoxia elevated [Ca2+]i and caused cell-shortening in 3 of 7 distal PASMCs. The correlation of hypoxia and 4-AP induced responses in distal and proximal pulmonary PASMCs, and the inhibition of hypoxic responses in some distal pulmonary PASMCs by 4-AP is consistent with the hypothesis. However, the presence of responses to 4-AP, but not hypoxia in femoral ASMCs. and the presence of hypoxic responses in some 4-AP treated distal pulmonary ASMCs, suggest that additional mechanisms may be involved in responses of porcine pulmonary ASMCs to hypoxia.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997

Fingerprint

4-aminopyridine
4-Aminopyridine
thighs
Thigh
smooth muscle
myocytes
Smooth Muscle Myocytes
Muscle
hypoxia
Swine
lungs
Cells
calcium
Lung
swine
cells
vasoconstriction
pulmonary artery
Vasoconstriction
potassium channels

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

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title = "Differential effects of hypoxia and 4-aminopyridine (4-AP) in intracellular [Ca2+] and cell-length in porcine distal and proximal pulmonary and femoral arterial smooth muscle cells (ASMCs)",
abstract = "Acute hypoxia is thought to cause vasoconstriction in pulmonary arteries, but relaxation in systemic arteries. It has been proposed that inhibition of 4-AP sensitive (delayed rectifier) K+ channels in pulmonary ASMCs mediate hypoxic pulmonary vasoconstriction. We tested this hypothesis by examining (1) whether there was a correlation between the hypoxia and 4-AP induced responses in porcine pulmonary and femoral ASMCs and (2) whether the hypoxic responses was altered by inhibiting delayed rectifier K+ channels. ASMCs were isolated enzymatically from proximal (> 1 cm o.d.) and distal (0.3-0.8 mm o.d.) intralobar pulmonary arteries and femoral arteries. [Ca2+], and cell-length of single freshly isolated ASMC were monitored simultaneously using Indo-1 AM and video-microscopy. A decrease in pO2 from 110 mmHg to <10 mmHg had no effect in femoral and poximal pulmonary ASMCs. but caused small but significant increases in [Ca2+] and decreases in cell-length in distal PASMCs. In contrast, 4-AP (10 mM) increased [Ca2+]i and decreased cell-length in distal pulmonary and femoral ASMCs, but had no significant effect in proximal pulmonary ASMCs. All three types of myocytes responded to KCl (100 mM) to a similar extent. In the presence of 10 mM 4-AP, hypoxia elevated [Ca2+]i and caused cell-shortening in 3 of 7 distal PASMCs. The correlation of hypoxia and 4-AP induced responses in distal and proximal pulmonary PASMCs, and the inhibition of hypoxic responses in some distal pulmonary PASMCs by 4-AP is consistent with the hypothesis. However, the presence of responses to 4-AP, but not hypoxia in femoral ASMCs. and the presence of hypoxic responses in some 4-AP treated distal pulmonary ASMCs, suggest that additional mechanisms may be involved in responses of porcine pulmonary ASMCs to hypoxia.",
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T1 - Differential effects of hypoxia and 4-aminopyridine (4-AP) in intracellular [Ca2+] and cell-length in porcine distal and proximal pulmonary and femoral arterial smooth muscle cells (ASMCs)

AU - Sham, James

AU - Crenshaw, B. R.

AU - Sylvester, J. T.

PY - 1997

Y1 - 1997

N2 - Acute hypoxia is thought to cause vasoconstriction in pulmonary arteries, but relaxation in systemic arteries. It has been proposed that inhibition of 4-AP sensitive (delayed rectifier) K+ channels in pulmonary ASMCs mediate hypoxic pulmonary vasoconstriction. We tested this hypothesis by examining (1) whether there was a correlation between the hypoxia and 4-AP induced responses in porcine pulmonary and femoral ASMCs and (2) whether the hypoxic responses was altered by inhibiting delayed rectifier K+ channels. ASMCs were isolated enzymatically from proximal (> 1 cm o.d.) and distal (0.3-0.8 mm o.d.) intralobar pulmonary arteries and femoral arteries. [Ca2+], and cell-length of single freshly isolated ASMC were monitored simultaneously using Indo-1 AM and video-microscopy. A decrease in pO2 from 110 mmHg to <10 mmHg had no effect in femoral and poximal pulmonary ASMCs. but caused small but significant increases in [Ca2+] and decreases in cell-length in distal PASMCs. In contrast, 4-AP (10 mM) increased [Ca2+]i and decreased cell-length in distal pulmonary and femoral ASMCs, but had no significant effect in proximal pulmonary ASMCs. All three types of myocytes responded to KCl (100 mM) to a similar extent. In the presence of 10 mM 4-AP, hypoxia elevated [Ca2+]i and caused cell-shortening in 3 of 7 distal PASMCs. The correlation of hypoxia and 4-AP induced responses in distal and proximal pulmonary PASMCs, and the inhibition of hypoxic responses in some distal pulmonary PASMCs by 4-AP is consistent with the hypothesis. However, the presence of responses to 4-AP, but not hypoxia in femoral ASMCs. and the presence of hypoxic responses in some 4-AP treated distal pulmonary ASMCs, suggest that additional mechanisms may be involved in responses of porcine pulmonary ASMCs to hypoxia.

AB - Acute hypoxia is thought to cause vasoconstriction in pulmonary arteries, but relaxation in systemic arteries. It has been proposed that inhibition of 4-AP sensitive (delayed rectifier) K+ channels in pulmonary ASMCs mediate hypoxic pulmonary vasoconstriction. We tested this hypothesis by examining (1) whether there was a correlation between the hypoxia and 4-AP induced responses in porcine pulmonary and femoral ASMCs and (2) whether the hypoxic responses was altered by inhibiting delayed rectifier K+ channels. ASMCs were isolated enzymatically from proximal (> 1 cm o.d.) and distal (0.3-0.8 mm o.d.) intralobar pulmonary arteries and femoral arteries. [Ca2+], and cell-length of single freshly isolated ASMC were monitored simultaneously using Indo-1 AM and video-microscopy. A decrease in pO2 from 110 mmHg to <10 mmHg had no effect in femoral and poximal pulmonary ASMCs. but caused small but significant increases in [Ca2+] and decreases in cell-length in distal PASMCs. In contrast, 4-AP (10 mM) increased [Ca2+]i and decreased cell-length in distal pulmonary and femoral ASMCs, but had no significant effect in proximal pulmonary ASMCs. All three types of myocytes responded to KCl (100 mM) to a similar extent. In the presence of 10 mM 4-AP, hypoxia elevated [Ca2+]i and caused cell-shortening in 3 of 7 distal PASMCs. The correlation of hypoxia and 4-AP induced responses in distal and proximal pulmonary PASMCs, and the inhibition of hypoxic responses in some distal pulmonary PASMCs by 4-AP is consistent with the hypothesis. However, the presence of responses to 4-AP, but not hypoxia in femoral ASMCs. and the presence of hypoxic responses in some 4-AP treated distal pulmonary ASMCs, suggest that additional mechanisms may be involved in responses of porcine pulmonary ASMCs to hypoxia.

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