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

被引:0
|
作者
Evlakhov, V. I. [1 ]
Poyassov, I. Z. [1 ]
Berezina, T. P. [1 ]
机构
[1] Inst Expt Med, St Petersburg, Russia
关键词
pulmonary thromboembolism; capillary filtration coefficient; ethosuximide; mibefradil; chloroquine; nifedipine; NORADRENALINE RELEASE; POTASSIUM CHANNELS; PHARMACOKINETICS; MIBEFRADIL; ARTERY; ETHOSUXIMIDE; HEMODYNAMICS; PERMEABILITY; VASODILATOR; CHLOROQUINE;
D O I
10.1134/S0022093023030195
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Changes in the pulmonary microhemodynamics in response toethosuximide, mibefradil, nifedipine, and chloroquine were studiedunder conditions of pulmonary thromboembolism in acute experimentson the isolated perfused lungs of the Chinchilla rabbits. In responseto T-type Ca2+ channel blockers ethosuximideand mibefradil, pulmonary artery pressure (PAP), precapillary resistance(R-a)and pulmonary vascular resistance (PVR) decreased approximatelyto the same extent, while postcapillary resistance (R-v) remainedintact. After chloroquine pretreatment, PAP, R-a,and PVR decreased to a greater extent than in response to ethosuximide, mibefradil,and L-type Ca2+ channel antagonist nifedipine; R-v also decreased.In the case of chloroquine administration combined with the infusionof the K-ATP channel blocker glibenclamide,most parameters of pulmonary microcirculation decreased nearly tothe same extent as in response to mibefradil, while R-v did notchange. After chloroquine pretreatment in response to pulmonaryembolization, PVR, R-a and R-v increasedto a lesser extent than with thromboembolism after pretreatmentswith ethosuximide, mibefradil and nifedipine. When modeling thromboembolismafter chloroquine pretreatment combined with the K-ATP channel blockerglibenclamide, the hemodynamic parameters increased to the sameextent as after nifedipine pretreatment. Thus, chloroquine exhibitsthe properties of L- and T-type Ca2+ channel blocker,as well as a K-ATP channel activator, whereasethosuximide has a blocking effect mainly on T-type Ca2+ channelsin pulmonary artery smooth muscle cells. The shifts in capillaryfiltration coefficient under the above conditions depend more onchanges in R-a thanon endothelial permeability of pulmonary vessels.
引用
收藏
页码:866 / 876
页数:11
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