Endothelin-1-induced oedema in rat and guinea-pig isolated perfused lungs.
Endothelin-1 caused an increase in perfusion pressure, bronchial resistance, lung weight and tracheal effusion when infused through the pulmonary artery of rat and guinea-pig isolated lungs. In contrast to vasoconstriction, the effects of endothelin-1 on bronchial resistance, lung weight and tracheal effusion were not concentration-dependent. Recovery from vasoconstriction occurred within 15-30 min when the lung was further perfused with Krebs buffer. Increases in lung weight, bronchial resistance and tracheal effusion induced by endothelin-1 were irreversible when infused at concentrations above 10(-10) M. UK 38,485, a thromboxane A2 synthesis inhibitor, partly prevented the increase in lung weight and tracheal effusion without altering the vasoconstriction induced by endothelin-1. Such an antagonism was not seen in guinea-pig lung at the concentration used. Iloprost, a stable analogue of prostacyclin, antagonized the effects of endothelin-1 on perfusion pressure and lung weight without reducing tracheal effusion in both rat and guinea-pig lungs. Pretreatment with allopurinol did not alter the effects of endothelin-1. These results were taken as evidence for the potent lung oedema-producing effect of the peptide which seems to be partially mediated by the secondary release of thromboxane A2.
Ercan
Z S
ZS
Department of Pharmacology, Faculty of Medicine, Gazi University, Turkey.
Kilinç
M
M
Yazar
O
O
Korkusuz
P
P
Türker
R K
RK
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004487:Edema / Q000139:chemically induced*; D016232:Endothelins / Q000009:adverse effects*; D005260:Female; D006168:Guinea Pigs; D016285:Iloprost / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D008171:Lung Diseases / Q000139:chemically induced; D008297:Male; D010477:Perfusion; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology
D016232:Endothelins; D007093:Imidazoles; D014665:Vasodilator Agents; C039242:dazmegrel; D000493:Allopurinol; D016285:Iloprost