Protective effects of G 619, a dual thromboxane synthase inhibitor and thromboxane A2 receptor antagonist, in splanchnic artery occlusion shock.
Splanchnic artery occlusion (SAO) shock was induced in anesthetized rats by clamping the celiac trunk and the superior mesenteric artery for 45 min. The arteries were then released and survival rate, mean survival time, mean arterial blood pressure (MAP), plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1 alpha, and the phagocytotic activity of peritoneal macrophages were evaluated. Shocked animals died within 89 +/- 10 min, while all sham-shocked rats survived greater than 3 h. SAO shock produced relevant changes in MAP, significantly increased plasma levels of TxB2 and 6-keto-PFG1 alpha, and decreased peritoneal macrophage phagocytotic activity. The administration of G 619, a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist (50 mg/kg, 15 min before SAO shock) significantly increased survival time (190 +/- 13 min) and survival rate, reduced plasma levels of TxB2, and partially restored the impairment in peritoneal macrophage phagocytosis. Finally, the administration of G 619 had beneficial effects on changes in MAP-induced bay SAO shock. These data further confirm the involvement of TxA2 in SAO shock and suggest that G 619 may have positive effects in low-flow states.
Squadrito
F
F
Institute of Pharmacology, University of Messina, Italy.
Altavilla
D
D
Zingarelli
B
B
Ioculano
M P
MP
Campo
G M
GM
Calapai
G
G
Saitta
A
A
Urna
G
G
Sardella
A
A
Spignoli
G
G
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications* / Q000503:physiopathology; D001549:Benzamides / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D008264:Macrophages / Q000502:physiology; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D010847:Picolines / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D012769:Shock / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001549:Benzamides; D010847:Picolines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C074732:3-carbamyl-(3'-picolyl)-4-methoxy-1-benzamide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase