Effect of T- and L-Type Calcium Channel Blockers on Pulmonary Microhemodynamics in a Rabbit Model of Pulmonary Thromboembolism

Changes in the pulmonary microhemodynamics in response to ethosuximide, mibefradil, nifedipine, and chloroquine were studied under conditions of pulmonary thromboembolism in acute experiments on the isolated perfused lungs of the Сhinchilla rabbits. In response to T-type Ca2+ channel blockers ethosuximide and mibefradil, pulmonary artery pressure (PAP), precapillary resistance (Ra) and pulmonary vascular resistance (PVR) decreased approximately to the same extent, while postcapillary resistance (Rv) remained intact. After chloroquine pretreatment, PAP, Ra, and PVR decreased to a greater extent than in response to ethosuximide, mibefradil, and L-type Ca2+ channel antagonist nifedipine; Rv also decreased. In the case of chloroquine administration combined with the infusion of the KATP channel blocker glibenclamide, most parameters of pulmonary microcirculation decreased nearly to the same extent as in response to mibefradil, while Rv did not change. After chloroquine pretreatment in response to pulmonary embolization, PVR, Ra and Rv increased to a lesser extent than with thromboembolism after pretreatments with ethosuximide, mibefradil and nifedipine. When modeling thromboembolism after chloroquine pretreatment combined with the KATP channel blocker glibenclamide, the hemodynamic parameters increased to the same extent as after nifedipine pretreatment. Thus, chloroquine exhibits the properties of L- and T-type Ca2+ channel blocker, as well as a KATP channel activator, whereas ethosuximide has a blocking effect mainly on T-type Ca2+ channels in pulmonary artery smooth muscle cells. The shifts in capillary filtration coefficient under the above conditions depend more on changes in Ra than on endothelial permeability of pulmonary vessels.