thromboxane-a2 and Poultry-Diseases

Endothelial injury caused by viruses usually involves viral replication or transformation. We report a novel mechanism of endothelial damage by a toxic viral protein. We have isolated a new retrovirus from hemangiosarcomas which appeared among layer hens. The isolated avian hemangiosarcoma virus (AHV) is capable of inducing hemangiomas in hens in-vivo and causes a cytopathic effect (CPE) and loss of thromboresistance in cultured bovine aortic endothelial cells (BAEC). These effects do not require viral replication and can be induced by purified AHV envelop glycoprotein (gp85). AHV causes CPE in BAEC through a typical programmed cell death (apoptosis). Quiescent G0/G1-BAEC are much more sensitive to AHV induced apoptosis than actively dividing cells. These experiments demonstrate the capacity of viral proteins to affect the integrity and functionality of vascular endothelial cells.

Topics: Animals; Aorta; Apoptosis; Avian Sarcoma Viruses; Cattle; Cell Cycle; Cells, Cultured; Chickens; Cytopathogenic Effect, Viral; Endothelium, Vascular; Extracellular Matrix; Hemangiosarcoma; Immunity, Innate; Poultry Diseases; Sarcoma, Avian; Thrombosis; Thromboxane A2; Viral Envelope Proteins

Bacterial endotoxins stimulate endothelin-mediated, thromboxane-dependent increases in pulmonary vascular resistance in mammals, and thromboxane has been shown to cause an immediate but transient pulmonary vasoconstriction in broiler chickens. In the present study, i.v. injections of 1 mg endotoxin into anesthetized male broilers caused a pulmonary vasoconstrictive response that was delayed in onset by 15 min and that elevated the pulmonary arterial pressure by 10 mm Hg within 25 min postinjection. Thereafter, pulmonary hemodynamic variables gradually (> or = 15 min) returned toward pre-injection levels, and supplemental injections of 4 mg endotoxin during this recovery period failed to reinitiate pulmonary hypertension. In contrast, injecting the thromboxane A2 mimetic U44069 during the endotoxin recovery period triggered pulmonary vasoconstriction and pulmonary hypertension similar in magnitude to the responses triggered by U44069 before endotoxin had been administered. The time course and magnitude of the pulmonary hemodynamic responses to endotoxin were highly variable among individual broilers, whereas the individual responses to U44069 were more consistent. Unanesthetized broilers resembled anesthetized broilers in the time course, magnitude, and variability of their pulmonary hemodynamic responses to endotoxin. Overall, these observations are consistent with the hypothesis that endotoxin initiates a biochemical cascade, culminating in the delayed onset of pulmonary vasoconstriction and pulmonary hypertension within 20 min postinjection. Subsequently, the pulmonary vasculature remains responsive to large bolus injections of exogenous thromboxane mimetic; however depletion of endogenous vasoconstrictive components of the endotoxin-mediated cascade, a compensatory increase in endogenous vasodilators, or the induction of a transient cellular tolerance to endotoxin prevented fourfold higher doses of endotoxin from reversing the return toward a normal pulmonary vascular tone. Individual differences among broilers in their susceptibility to pulmonary hypertension syndrome (ascites) may be related to innate or acquired variability in their pulmonary vascular responsiveness to vasoactive mediators.

Topics: Animals; Chickens; Endotoxins; Hypertension, Pulmonary; Injections, Intravenous; Male; Poultry Diseases; Prostaglandin Endoperoxides, Synthetic; Pulmonary Circulation; Thromboxane A2; Vascular Resistance; Vasoconstriction