Effects of intracellular pH on hypoxic vasoconstriction in rat lungs.
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.
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
B
B
Raffestin
I F
IF
McMurtry
D000085:Acetates / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D003593:Cytoplasm / Q000032:analysis; D006531:HEPES / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D066298:In Vitro Techniques; D008168:Lung / Q000503:physiopathology*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014661:Vasoconstriction
D000085:Acetates; D001639:Bicarbonates; D000643:Ammonium Chloride; D000584:Amiloride; D013755:Tetradecanoylphorbol Acetate; D006531:HEPES