Effects of verapamil on thromboxane synthesis and pulmonary hypertension in sheep

Infusion of plasma containing zymosan-activated complement into sheep produces leukopenia, pulmonary leukostasis, pulmonary hypertension, hypoxia and increased plasma levels of thromboxane. We investigated the effects of the calcium channel blocking agent verapamil in this system using conscious sheep. Verapamil in 5 mg and 10 mg doses was administered by intravenous infusion prior to an infusion of autologous plasma containing zymosan-activated complement. Pretreatment with verapamil inhibited thromboxane synthesis, the rise in pulmonary artery pressure and the hypoxia without affecting the transient leukopenia. These effects are similar to those previously demonstrated with nonsteroidal antinflammatory drugs, suggesting that verapamil is acting at one or more early steps of the arachidonic acid cascade in addition to its influence on the calcium-sensitive protein interactions involved in smooth muscle function.