DISTURBANCES IN EX-VIVO VASCULAR SMOOTH-MUSCLE RESPONSES FOLLOWING EXPOSURE TO PASTEURELLA-HAEMOLYTICA VACCINES

Rats were vaccinated with saline (control) or one of the two commercia lly available Pasteurella haemolytica vaccines Presponse or Precon-PH. Animals were killed 3 days later and thoracic aorta removed for evalu ation of the ex vivo biophysical responses to carbachol (CCh). In some experiments, vascular endothelium was mechanically removed. Vaccinati on of rats impairs the endothelial-dependent relaxation to CCh. In ves sels with endothelium removed, the contractile response to CCh is conv erted into a relaxation following vaccination. Treatment of endothelia l-denuded vascular rings ex vivo with methylene blue, a guanylate cycl ase inhibitor, reduced the vaccination effect. Treatment of vascular r ings with the superoxide dismutase inhibitor diethyldithiocarbamate, i mpairs the relaxant reponse of de-endothelialized vessels to CCh in Pr esponse vaccinated rats while enhancing the relaxation response of ves sels from Precon-PH vaccinated rats. De-endothelialized vessels from v accinated rats, but not control rats, relaxed in the presence of N-mon omethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide s ynthetase. Furthermore, in the presence of L-NMMA, the relaxant respon se to CCh is significantly enhanced by Precon-PH but not Presponse. Th e normal relaxant response to hydrogen peroxide is converted into a co ntraction following vaccination. Results suggest that exposure to comm ercially available P. haemolytica vaccines alters vascular smooth musc le reactivity to CCh and that several independent pathways may be alte red.