The role of activated neutrophils and free radical in the pathogenesis of pulmonary hypertension.

In in situ perfused rat lungs, it was demonstrated that the perfusing pressure and permeability of pulmonary capillaries were obviously increased after activated neutrophils (PMNs) were added to the perfusate. The effect of free radicals generated by the xanthine-xanthine oxidase system on isolated rabbit pulmonary arterial ring tension was also observed, and the contractile response was found to be dose dependent: The smaller the vessel diameter, the higher the contractile response. Superoxide dismutase and catalase were able to obviously attenuate the contractile response. The response was endothelium independent, and was influenced neither by indomethacin (cyclooxygenase inhibitor) nor by nordihydroguaiaretic acid (lipoxygenase inhibitor), while removal of Ca from the bath solution or addition of the protein kinase C (PKC) inhibitor "H7" or an antiinflammatory drug (764-3, the effective component of Radix Salvia miltiorrhizae) could significantly inhibit the contractile response. The results suggest that activated PMNs may play an important role in the pathogenesis of pulmonary hypertension.