VARIABLE EFFECTS OF HUMAN AND CANINE POLYMORPHONUCLEAR LEUKOCYTES ON VASCULAR SMOOTH-MUSCLE TONE

Objective: Previous studies have shown variable effects of human and canine polymorphonuclear leucocytes (neutrophils) on vascular tone. The aim of this study was to identify whether these variations in neutrophil function are due to species differences. Methods: Canine and human arterial rings (with and without endothelium) were contracted with the thromboxane A2 analogue U46619, and then exposed to isolated neutrophils. Results: Human neutrophils caused a significant relaxation of the human mammary arterial rings, and the relaxation was unaffected by the cyclo-oxygenase inhibitor indomethacin, enhanced by superoxide dismutase (SOD), and inhibited by oxyhaemoglobin. The relaxant effect of human neutrophils was also diminished upon pretreatment with N(G)-monomethyl-1-arginine (L-NMMA), indicating that the vasorelaxant material released by the neutrophils was nitric oxide (NO). Human neutrophils also relaxed canine femoral arterial rings, and the relaxant effect was potentiated by SOD and inhibited by pretreatment with oxyhaemoglobin or L-NMMA, confirming that the vasorelaxation was via release of NO. Canine neutrophils, on the other hand, caused an endothelium dependent contraction of autologous femoral arterial rings. This vasoconstriction was not affected by indomethacin, SOD, Oxyhaemoglobin, or L-NMMA. However, treatment of canine neutrophils with the 5-lipoxygenase inhibitor piriprost attenuated (p<0.02) their contractile effect on vascular rings, suggesting that neutrophil generated 5-lipoxygenase products were probably responsible for smooth muscle contraction. Presence of the leukotriene C4 and D4 receptor antagonist FPL 55,712 totally blocked the contractile effects of canine neutrophils, indicating that femoral arterial ring contraction was mediated by peptido-leukotrienes. Conclusions: The endothelium dependent nature of the canine neutrophil induced contraction suggests that the 5-lipoxygensase product leukotriene A4 is taken up by endothelial cells for conversion to peptido-leukotrienes. Since SOD had no effect and FPL 55,712 totally blocked the vasoconstrictor effects of canine neutrophils, it appears that the vasoconstrictor effects of the latter are mediated primarily through peptido-leukotrienes. In contrast, the vasorelaxation by human neutrophils is mediated through release Of NO.