Platelet-activating factor raises airway and vascular pressures and induces edema in lungs perfused with platelet-free solution.
The effects of synthetic platelet-activating factor (PAF) on guinea pig lung were examined in isolated lungs perfused with platelet-free Krebs-Ringer solution. When PAF (1 microgram) was injected into the pulmonary artery (PA), it markedly increased airway pressure (maximal increase, 84.7%) and moderately raised PA pressure (maximal increase, 22.8%). The same dose also provoked a massive (29-fold) release of thromboxane B2 (TXB2), the stable metabolite of TXA2, into the perfusate, beginning before the increases in airway and PA pressures. The concentration of 6 keto-PGF1 alpha, the stable metabolite of prostacyclin, also increased (to 5 times control levels) about 70 s after peak release of TXB2. Indomethacin completely blocked TXB2 release, reduced the magnitude of airway pressure increase by 79%, and shortened its duration, as well as the duration of the PA pressure rise. Larger concentrations of PAF (3 and 10 micrograms) produced even greater increments in airway and PA pressures, but these were only moderately attenuated by indomethacin. Also, PAF increased extravascular lung water, as evidenced by increases in wet/dry lung weight and lung/body weight ratios. In a concentration of 0.1 microgram, PAF had no effects on airway or PA pressures, nor did it stimulate TXB2 or 6-keto-PGF1 alpha release. Lyso-PAF was similarly ineffective. We conclude that PAF induces airway constriction, pulmonary hypertension, and pulmonary edema in guinea pig lung independently of platelets. These effects are associated with stimulated synthesis of TXA2, but the mechanisms of their production remain to be determined.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000403:Airway Resistance; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D010477:Perfusion; D010972:Platelet Activating Factor / Q000502:physiology*; D011312:Pressure; D011654:Pulmonary Edema / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000096:biosynthesis; D014655:Vascular Resistance
D010972:Platelet Activating Factor; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin