VACCINATION WITH LIVE PASTEURELLA-HAEMOLYTICA ALTERS CHOLINERGIC RESPONSES OF PULMONARY BLOOD-VESSELS - PASTEURELLA VACCINATION ALTERS PULMONARY VASOREACTIVITY

Sheep were injected (i.m.) with a live vaccine-derived strain of Paste urella haemolytica. Three days later, intrapulmonary artery and vein w ere removed for determination of the ex vivo concentration response cu rve to carbachol (CCh). In pulmonary artery from control (saline injec ted) animals, removal of the endothelium shifts the calculated thresho ld and pD2 to the left while reducing the maximum relaxation attained in response to CCh. In pulmonary artery from P. haemolytica vaccinated sheep the calculated threshold, pD2 and maximum relaxation attained i s similar to that in control animals following removal of the endothel ium. Mechanical removal of the endothelium in pulmonary artery from va ccinated animals does not significantly alter the concentration respon se curve to CCh. Preincubation of endothelial intact pulmonary artery from control or vaccinated animals with indomethacin did not alter the calculated threshold or pD2. On the other hand, in control, but not v accinated animals, indomethacin treatment reduced the maximum relaxati on attained. In pulmonary vein from control animals, CCh causes a low dose relaxant response with contractions occurring at higher concentra tions. Mechanical removal of the endothelium eliminates the low dose r elaxant response without altering the contractile response to CCh. Pre incubation of endothelial-intact pulmonary vein from control animals w ith indomethacin shifts the calculated threshold to the left without a ltering the pD2 or maximum tension attained. In pulmonary vein from va ccinated animals, the low dose relaxant response is eliminated irrespe ctive of the presence of endothelium. Preincubation of endothelial-int act pulmonary vein from vaccinated animals with indomethacin shifts th e calculated threshold and pD2 to the left and reduces the maximum con tractile response. Scanning electron microscopy of the endothelial cel l surface indicates that vaccination causes cell surface 'blebs', sugg esting cellular irritation. These data support the hypothesis that vac cination with live P haemolytica alters endothelial dependent response s of pulmonary vessels during the post-vaccination period. It is sugge sted that such sub-clinical disturbances may contribute to initiation of clinical disease.