The prominent role of thromboxane A2 formation on early pulmonary hypertension induced by oleic acid administration in sheep.
The early increase of pulmonary artery pressure observed in different models of experimentally induced lung injury have been shown to be associated with the release of vasoconstrictive agents by activated platelets. The aim of this study was to evaluate the pattern of these metabolites, in particular TxA2, and the effects of the inhibition of their production by ASA on the modifications of pulmonary hemodynamics induced by oleic acid administration in sheep. Group I (8 sheep) was infused with oleic acid (0.09 ml/kg at 0.02 ml/min) while in group II (6 sheep) ASA (10 mg/kg i.v.) was administered 30 minutes before oleic acid infusion. In group I pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were significantly higher at the end of the infusion while cardiac output (CO) significantly decreased in comparison to baseline values. A marked increase in plasma TxB2 levels paralleled pulmonary hemodynamic changes. Also plasma 6 keto PGF levels increased after OA infusion. The early increase in PAP and PVR was significantly lower in group II (p less than 0.005) while CO did not undergo any significant change. ASA pretreatment significantly blunted the rise of TxB2 concentrations and prevented the elevation of 6 keto PGFa. These results indicate that early pulmonary hypertension in oleic acid induced injury is mainly related to TxA2 released from platelets and leukocytes and that pulmonary hemodynamic changes are significantly inhibited by ASA pretreatment.
Rostagno
C
C
Clinica Medica I, University of Florence, Italy.
Gensini
G F
GF
Boncinelli
S
S
Marsili
M
M
Castellani
S
S
Lorenzi
P
P
Merciai
V
V
Linden
M
M
Chelucci
G L
GL
Cresci
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects; D019301:Oleic Acid; D009829:Oleic Acids; D012756:Sheep; D013928:Thromboxane A2 / Q000096:biosynthesis*; D014655:Vascular Resistance / Q000187:drug effects
D009829:Oleic Acids; D019301:Oleic Acid; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D001241:Aspirin