The role of thromboxane in cuprophan-induced pulmonary hypertension.

Previous studies demonstrated that acute infusion of cuprophan activated plasma into experimental animals produce cardiopulmonary changes which included severe pulmonary hypertension. It was further suggested that these changes were mediated by complement activation products. The current study examined the role of arachidonic acid metabolites in the pathogenesis of cuprophan-induced pulmonary hypertension in the swine. Plasma thromboxane concentrations and pulmonary arterial pressure rose concomitantly with cuprophan-activated plasma infusion; both could be inhibited by the specific thromboxane synthetase inhibitor, OKY1581. Likewise, this inhibitor also blocked the increment in plasma thromboxane concentrations and pulmonary arterial pressure induced by zymosan-activated plasma. In vitro incubation of cuprophan-activated plasma with porcine lung fragments produced significantly higher thromboxane concentrations in the medium than incubation with other porcine tissues examined. It is postulated that the complement activation products formed in the plasma during cuprophan exposure subsequently stimulated release of thromboxane from the lungs and other tissues upon infusion of the plasma into animals. The thromboxane, in turn, triggers the pulmonary hypertension.

Ethanol and temperature effects on five membrane bound enzymes.

The effects of ethanol on the activities of five membrane bound enzymes were determined using a crude membrane preparation obtained from cortex of long-sleep (LS) and short-sleep (SS) mice. These two mouse lines were selectively bred for differences in duration of ethanol-induced sleep time. The enzymes studied were two forms of NaK-ATPase, Mg-ATPase, 5'nucleotidase, and acetylcholinesterase. Arrhenius plots of the ethanol-temperature-enzyme activity studies indicate specificity in ethanol's actions. NaK-ATPase activity consists of two enzymes which were distinguished by sensitivity to ouabain. The Arrhenius plot of the high ouabain sensitivity enzyme (low Ki) exhibited a transition temperature which was reduced twice as much by ethanol in LS membranes as in SS membranes. Ethanol did not affect the transition temperature of the high Ki NaK-ATPase but the control (no ethanol) transition temperature was 2.7 degrees higher in SS membranes. Arrhenius plots of Mg-ATPase activity did not exhibit a transition temperature and ethanol did not alter enzyme activity. Ethanol did not alter the transition temperatures of 5'nucleotidase or acetylcholinesterase but the control transition temperature for acetylcholinesterase was 2.3 degrees higher in SS membranes. These results indicate specificity in ethanol's actions on membranes and that inhibition of the lipid-enzyme interactions for the low Ki NaK-ATPase is correlated with the difference in sensitivity to ethanol seen between the LS and SS mice.