Thromboxane increases pulmonary vascular resistance and transvascular fluid and protein exchange after pulmonary microembolism.
We compared the effects of inhibition of thromboxane synthetase with antagonism of thromboxane A2 (TxA2)/prostaglandin H2 receptors on the changes in pulmonary hemodynamics and pulmonary transvascular fluid and protein exchange following thrombin-induced pulmonary microembolism. Studies were made in chronically instrumented unanesthetized sheep prepared with lung lymph fistulas. Control thrombin challenged sheep (n = 5) were compared to animals pretreated with Dazoxiben (the Dazoxiben-thrombin group, n = 8) or animals pretreated with L-640,035 (the L-640,035-thrombin group, n = 5). In the control-thrombin sheep, plasma TxA2 concentration rose after thrombin and the response was inhibited in the Dazoxiben-thrombin group. The rise in the plasma TxA2 concentration was greater in the L-640,035-thrombin group than in the control-thrombin group. In the control-thrombin group, thrombin produced a sustained increase in the pulmonary transvascular protein clearance (pulmonary lymph flow x lymph/plasma protein concentration ratio) and pulmonary vascular resistance (PVR). In the Dazoxiben-thrombin group, increases in both pulmonary transvascular protein clearance and PVR after thrombin were less than in the control-thrombin group. In the L-640,035-thrombin group, thrombin initially increased pulmonary transvascular protein clearance and PVR to the same levels as the control group; however, both protein clearance and PVR declined with time, in contrast to the sustained responses in the control-thrombin group. These differences may be related to the initially greater increase in plasma TxA2 concentrations after thrombin in the L-640,035-treated animals. The results indicate that TxA2 plays a role in mediating the increases in PVR and contributes to increases in pulmonary transvascular fluid and protein exchange after thrombin-induced pulmonary microembolism.
Garcia-Szabo
R
R
Department of Physiology, Albany Medical College, New York.
Johnson
A
A
Malik
A B
AB
D000818:Animals; D001834:Body Water / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D011506:Proteins / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects; D011655:Pulmonary Embolism / Q000378:metabolism / Q000503:physiopathology*; D012756:Sheep; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects*
D007093:Imidazoles; D011506:Proteins; C029166:dazoxiben; D013928:Thromboxane A2; D013917:Thrombin