Journal of Applied Physiology, Vol 67, Issue 1 44-51, Copyright © 1989 by American Physiological Society
Role of thromboxane receptors in Forssman shock in guinea pigs
W. A. Schumacher, T. E. Steinbacher, G. T. Allen and M. L. Ogletree
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
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.
