Comparative Responses to Leukotriene D4 in the Sheep and Cat
Pulmonary vascular responses to leukotriene (LT) D4 were compared in the sheep and cat under conditions of controlled lobar blood flow. Intralobar injections of LTD4 in the sheep caused dose-dependent increases in lobar arterial and small vein pressures without influencing left atrial or systemic arterial pressure. Leukotriene D4 was very potent in increasing pulmonary vascular resistance in the sheep, with activity similar to U-46619, a thromboxane (Tx) A2 mimic. Pulmonary vascular responses to LTD4 in the sheep were similar when the lung was ventilated and when lobar ventilation was arrested and when the lobe was perfused with blood or with dextran. Pulmonary vasoconstrictor responses to LTD4 but not to U-46619 in the sheep were reduced by inhibitors of cyclooxygenase and thromboxane synthesis. In contrast, LTD4 had modest pressor activity in the pulmonary vascular bed of the cat, whereas U-46619 had marked activity in this species. Responses to LTD4 in the cat were not altered by cyclooxygenase inhibitors.
It is concluded that LTD4 has marked pulmonary vasoconstrictor activity in the sheep, increasing pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In this species, responses to LTD4 were independent of changes in ventilation or the interaction with formed elements but were dependent on the formation of cyclooxygenase products including TxA2. However, in the cat, LTD2 had very weak pressor activity, and this activity was not dependent on the integrity of the cyclooxygenase system. These studies indicate that there is considerable species difference in responses to LTD4, a major component of the slow reacting substance of anaphylaxis, in the pulmonary vascular bed.
KeywordsArachidonic Acid Pulmonary Vascular Resistance Systemic Arterial Pressure Left Atrial Pressure Cyclooxygenase Inhibitor
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