Vanadate potentiates hypoxic pulmonary vasoconstriction.
Vanadate, an essential trace element and an inhibitor or stimulator of many enzymes, potentiates the hypoxic vasoconstriction in isolated lung preparations. However, the mechanism of action of vanadate in the lung circulation is unclear. We compared, in isolated rat lungs, the effect of vanadate (3 x 10(-5) M) on hypoxia-induced vasoconstriction with the vasoconstriction caused by angiotensin II, KCl or NaCN, and found that vanadate preferentially enhanced the hypoxia- and NaCN-induced pressor responses. Vanadate also shifted the stimulus-response curve for oxygen such that vasoconstriction occurred at a higher PO2 than in control lungs, indicating that vanadate had affected the oxygen sensing mechanism in the lungs. We postulated that vanadate might potentiate hypoxic vasoconstriction, in part, by activating a protein kinase C (PKC), and compared the effect of phorbol myristate acetate (PMA; 5 x 10(-8) M) on hypoxic vasoconstriction with that of vanadate. Both agents, PMA and vanadate, potentiated hypoxic vasoconstriction transiently and to a similar degree and the potentiation by both agents was blocked by staurosporine (1 microgram/ml), a PKC inhibitor, and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, a phospholipase C inhibitor, and partially reduced by the Ca++ entry inhibitor nifedipine. We conclude that the similarities between the action of PMA and vanadate in isolated lungs point toward an involvement of the PKC in the mechanism of vanadate-induced potentiation of hypoxic vasoconstriction. In addition, our data indicate that potentiation of hypoxic vasoconstriction by PMA or vanadate may occur, in part, independent of voltage-dependent Ca++ entry.
Voelkel
N F
NF
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver.
Czartolomna
J
J
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002219:Carbamates / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003486:Cyanides; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000502:physiology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D048448:Phenylcarbamates; D011651:Pulmonary Artery; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D002219:Carbamates; D003486:Cyanides; D048448:Phenylcarbamates; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D014638:Vanadates; D002374:Catalase; D013482:Superoxide Dismutase; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen