MINIREVIEW

Changes in Smooth Muscle Cell pH during Hypoxic Pulmonary Vasoconstriction: A Possible Role for Ion Transporters

J. A. Madden^1,2, P. A. Keller², J. G. Kleinman^2,3

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 (pH_i). SMC from large pulmonary arteries (LPA) relax during hypoxia, and [Ca²⁺]_i and pH_i decrease. Increases in pH_i 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 pH_i 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 pH_i in the presence of CO₂ and HCO₃^–. Inhibiting the Cl^–/HCO₃^– transporters reversed the normal direction of pH_i change during hypoxia, suggesting a role for these transporters in the hypoxic response. Future studies to determine the interaction between pH_i, [Ca²⁺]_i and HPV should ascertain whether pH_i 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