Changes in smooth muscle cell pH during hypoxic pulmonary vasoconstriction: A possible role for ion transporters

Hypoxic pulmonary vasoconstriction (HPV) occurs in smooth muscle cells (SMC ) from small pulmonary arteries (SPA) and is accompanied by increases in fr ee cytoplasmic calcium ([Ca2+](i)) and cytoplasmic pH (pH(i)). SMC from lar ge pulmonary arteries (LPA) relax during hypoxia, and [Ca2+](i) and pH(i) d ecrease. Increases in pH(i) and [Ca2+](i) in cat SPA SMC during hypoxia and the augmentation of hypoxic pulmonary vasoconstriction by alkalosis seen i n isolated arteries and lungs suggest that cellular mechanisms, which regul ate inward and outward movement of Ca2+ and H+, may participate in the gene ration 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- transp orters which regulate intracellular chloride. The Na+-dependent Cl-/HCO3- t ransporter also aids in recovery from acidosis in the presence of CO2 and H CO3-. The Na+-independent Cl-/HCO3- transporter aids in recovery from cellu lar alkalosis. The Na+-H+ transporter was present in SMC from SPA and LPA o f the cat, but it seemed to have little if any role in regulating pHi in th e presence of CO2 and HCO3-. Inhibiting the Cl-/HCO3- transporters reversed the normal direction of pHi change during hypoxia, suggesting a role for t hese 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 i nhibit SMC contraction.