Lung protection against paraquat is calcium dependent.
Isolated, perfused, and ventilated rat lungs were challenged by paraquat (0.01 M) in the presence of 2.5 mM Ca2+, 2.5 mM Ca2+ with trifluoperazine (100 microM), 0.025 mM Ca2+, or 0.025 mM Ca2+ with sodium metavanadate (10 microM) to establish the effect of varying calcium concentration or calcium-dependent enzyme activities on injury induced by paraquat. Segmental vascular resistances, microvascular permeability (as assessed by the capillary filtration coefficient), lung tissue oxidized glutathione, and lung paraquat accumulation were measured. Exposure to paraquat for 2.5 h did not increase microvascular permeability or pulmonary vascular resistance in the presence of either normal extracellular calcium or low extracellular calcium and sodium metavanadate. Lungs exposed to paraquat were injured (as assessed by increased filtration coefficient) only in the presence of low extracellular calcium or after trifluoperazine was added. This injury was associated with decreased levels of oxidized glutathione and increased paraquat accumulation, suggesting that calcium's protective effect was both by inhibition of paraquat accumulation and maintenance of NADPH. Pulmonary vascular resistance was not increased with paraquat challenge.
Barnard
J W
JW
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
Womack
W A
WA
Smith
S M
SM
Engerson
T D
TD
Taylor
A E
AE
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D055370:Lung Injury; D008297:Male; D009249:NADP / Q000378:metabolism; D010269:Paraquat / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D014268:Trifluoperazine; D009249:NADP; D005978:Glutathione; D010269:Paraquat; D002118:Calcium