Depolarization-dependent contraction increase after birth and preservation following long-term hypoxia in sheep pulmonary arteries.

Pulmonary Circulation
Demosthenes G PapamatheakisSean M Wilson

Abstract

Membrane depolarization is critical to pulmonary arterial (PA) contraction. Both L-type Ca(2+) channels (Ca(L)) and Rho-kinase are important signaling components of this process and mitochondrial and non-mitochondrial generated superoxides can be part of the signaling process. Maturation and long-term hypoxia (LTH) each can modify depolarization-dependent contraction and the role of superoxides. By the use of wire myography, we tested the hypothesis that maturation and LTH increase pulmonary arterial reactivity to high-K(+)-induced membrane depolarization through enhancements in the importance of Ca(L)and Rho-kinase-dependent pathways. The data show that maturation, but not LTH, increases contraction to 125 mM KCl (high-K(+)) without altering the EC(50). High-K(+)-dependent contraction was inhibited to a similar extent in fetal and adult PA by multiple Ca(L) blockers, including 10 μM diltiazem, 10 μM verapamil, and 10 μM nifedipine. Postnatal maturation increased the role for 10 μM nifedipine-sensitive Ca(L), and decreased that for 10 μM Y-27632-sensitive Rho-kinase. In all groups, the combination of nifedipine and Y-27632 effectively inhibited high-K(+) contraction. Tempol (3 mM) but not 100 μM apocynin slightly reduced contra...Continue Reading

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Citations

Jul 10, 2014·Pulmonary Circulation·Demosthenes G PapamatheakisSean M Wilson
Nov 24, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Christine P ShenSean M Wilson
May 3, 2018·Physiological Reviews·Charles A DucsayLubo Zhang
Mar 8, 2018·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Carla Blum-JohnstonSean M Wilson
Sep 11, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Scott R HadleySean M Wilson
Aug 21, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sebastián Castillo-GalánRoberto V Reyes
Nov 16, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Arlin B BloodSean M Wilson
Dec 8, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·Carla Blum-JohnstonSean M Wilson

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Methods Mentioned

BETA
GTPase
electrophoresis

Software Mentioned

ImageJ
Prism
GraphPad Prism
IGOR Pro
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