Isolated rat lungs perfused with physiological
salt-
Ficoll solutions were studied to test whether hypoxic pulmonary vasoconstriction was potentiated by increases in intracellular pH (pHi) and blunted by decreases in pHi. Whereas addition to perfusate of 5 nM
phorbol myristate acetate (PMA), a stimulator of exchange of intracellular H+ for extracellular Na+, potentiated hypoxic vasoconstriction, 1 mM
amiloride, an inhibitor of Na+-H+ exchange, blunted the hypoxic response. Hypoxic vasoconstriction was also potentiated by the weak bases NH4Cl (20 mM),
methylamine (10 mM), and
imidazole (5 mM) and was inhibited by the weak
acid sodium acetate (40 mM). NH4Cl,
imidazole, and
acetate had the same effects on KCl-induced vasoconstriction and on the hypoxic response. Hypoxic vasoconstriction was greater in lungs perfused with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic
acid (
HEPES)-buffered
solution than in those perfused with CO2/HCO3--buffered
solution. Similarly, lungs perfused with CO2/HCO3--buffered
solution containing 1.8 mM Cl- (NaNO3 and KNO3 substituted for NaCl and KCl) had larger hypoxic and
angiotensin II pressor responses than those perfused with 122.5 mM Cl-. Because PMA, NH4Cl,
methylamine,
imidazole,
HEPES-buffered solutions, and low-Cl- solutions can cause increases in pHi and
amiloride and
acetate can cause decreases in pHi, these results suggest that intracellular
alkalosis and
acidosis, respectively, potentiate and blunt
vasoconstrictor responses to
hypoxia and other stimuli in isolated rat lungs. These effects could be related to pHi-dependent changes in either the sensitivity of the arterial smooth muscle contractile machinery to Ca2+ or the release of a vasoactive mediator or modulator by some other lung cell.