MINIREVIEW
Changes in Smooth Muscle Cell pH during Hypoxic Pulmonary Vasoconstriction: A
Possible Role for Ion Transporters
J. A. Madden1,2, P. A. Keller2, J. G. Kleinman2,3
Departments of Neurology1 and Medicine3,
The Medical College of Wisconsin, and Research Service2,
Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin, U.S.A.
Received February 29, 2000
Accepted April 3, 2000
Summary
Hypoxic pulmonary vasoconstriction (HPV) occurs in smooth
muscle cells (SMC) from small pulmonary arteries (SPA) and is accompanied by
increases in free cytoplasmic calcium ([Ca2+]i) and cytoplasmic pH (pHi). SMC from large pulmonary arteries (LPA) relax
during hypoxia, and [Ca2+]i and pHi decrease.
Increases in pHi and [Ca2+]i in cat SPA SMC
during hypoxia and the augmentation of hypoxic pulmonary vasoconstriction by
alkalosis seen in isolated arteries and lungs suggest that cellular mechanisms,
which regulate inward and outward movement of Ca2+ and H+,
may participate in the generation of HPV. SMC transport systems that regulate pHi
include the Na+-H+ transporter which regulates
intracellular Na+ and H+ and aids in recovery from acid
loads, and the Na+-dependent and Na+-independent Cl–/HCO3–
transporters which regulate intracellular chloride. The Na+-dependent
Cl–/HCO3– transporter also aids in recovery
from acidosis in the presence of CO2 and HCO3–.
The Na+-independent Cl–/HCO3–
transporter aids in recovery from cellular alkalosis. The Na+-H+
transporter was present in SMC from SPA and LPA of the cat, but it seemed to
have little if any role in regulating pHi in the presence of CO2
and HCO3–. Inhibiting the Cl–/HCO3–
transporters reversed the normal direction of pHi change during
hypoxia, suggesting a role for these transporters in the hypoxic response.
Future studies to determine the interaction between pHi, [Ca2+]i
and HPV should ascertain whether pHi and [Ca2+]i
changes are linked and how they may interact to promote or inhibit SMC
contraction.
Key words
Cat ● Na+/H+ exchange ● Na+-dependent
Cl–/HCO3– exchange ● Na+-independent
Cl–/HCO3– exchange ● pH ● H+
ion
Reprint requests
Jane A. Madden, Ph.D., Neurology Research 151, VAMC,
Milwaukee, WI 53295, USA, fax (414) 382-5374, e-mail: jmadden@mcw.edu
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