Role of thromboxane receptors in Forssman shock in guinea pigs.
Forssman shock is a bronchospastic reaction mounted in guinea pigs on intravenous administration of an antiserum obtained from rabbits immunized against sheep erythrocytes. The involvement of thromboxane receptors in Forssman shock was determined with SQ 30,741, which was characterized as a selective antagonist of these receptors in guinea pig airways in vitro and in vivo. A volume of antiserum producing consistent, sublethal bronchoconstriction was given either alone (control) or 3 min after SQ 30,741 (0.03, 0.3, or 1.0 mg/kg iv) to urethan-anesthetized guinea pigs. In controls, maximum reductions in dynamic compliance (-59 +/- 6%, P less than 0.01) and increases in airways resistance (383 +/- 97%, P less than 0.01) were detected 1 min after antiserum. Both responses were significantly inhibited by SQ 30,741, either partially at 0.03 mg/kg or completely at 0.3 mg/kg. An accompanying thrombocytopenia was not abated by SQ 30,741. In separate experiments, bronchospasm was reduced by aerosol administration of 0.1% SQ 30,741 and completely prevented by aspirin (10 mg/kg iv). When Forssman antiserum was injected in lethal quantities to other guinea pigs, SQ 30,741 (1 mg/kg iv) attentuated only the resistance component of bronchospasm and did not prevent death. These data demonstrate that thromboxane receptor stimulation is a pivotal step in the pulmonary manifestations of sublethal Forssman shock but is less crucial in more severe forms of the reaction.
Schumacher
W A
WA
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
Steinbacher
T E
TE
Allen
G T
GT
Ogletree
M L
ML
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D001986:Bronchial Spasm / Q000276:immunology* / Q000503:physiopathology; D005577:Forssman Antigen / Q000276:immunology*; D006168:Guinea Pigs; D008297:Male; D011982:Receptors, Prostaglandin / Q000502:physiology*; D017482:Receptors, Thromboxane; D012769:Shock / Q000276:immunology* / Q000503:physiopathology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology
D015478:Antigens, Heterophile; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2; D005577:Forssman Antigen