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 commercially available Pasteurella haemolytica vaccines Presponse or Precon-PH. Animals were killed 3 days later and thoracic aorta removed for evaluation of the ex vivo biophysical responses to carbachol (CCh). In some experiments, vascular endothelium was mechanically removed. Vaccination of rats impairs the endothelial-dependent relaxation to CCh. In vessels with endothelium removed, the contractile response to CCh is converted into a relaxation following vaccination. Treatment of endothelial-denuded vascular rings ex vivo with methylene blue, a guanylate cyclase inhibitor, reduced the vaccination effect. Treatment of vascular rings with the superoxide dismutase inhibitor diethyldithiocarbamate, impairs the relaxant response of de-endothelialized vessels to CCh in Presponse vaccinated rats while enhancing the relaxation response of vessels from Precon-PH vaccinated rats. De-endothelialized vessels from vaccinated rats, but not control rats, relaxed in the presence of N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthetase. Furthermore, in the presence of L-NMMA, the relaxant response to CCh is significantly enhanced by Precon-PH but not Presponse. The normal relaxant response to hydrogen peroxide is converted into a contraction following vaccination. Results suggest that exposure to commercially available P. haemolytica vaccines alters vascular smooth muscle reactivity to CCh and that several independent pathways may be altered.