COMPARISON OF VASCULAR AND RESPIRATORY EFFECTS OF ENDOTHELIN-1 IN THEPIG

THE haemodynamic and respiratory responses caused by i.v. administrati on of endothelin-1 (ET-1) (20-100 pmol/kg) were studied in anaesthetiz ed spontaneously breathing pigs. Intravenous bolus administration of s ynthetic ET-1 (40-100 pmol/kg) caused a transient decrease followed by a long-lasting increase in mean pulmonary arterial pressure and dose dependent vasoconstriction both in the systemic and pulmonary circulat ions. The effect on pulmonary arterial pressure was biphasic, with an initial transient fall followed by a long-lasting dose dependent incre ase. A biphasic response of the systemic mean arterial pressure was de monstrated only at a high dose of ET-1 (100 pmol/kg). ET-1 administrat ion did not significantly change breathing pattern or phasic vagal inp ut, but caused a significant decrease in passive compliance. Passive r esistances or active compliance and resistances of the respiratory sys tem were not modified. These results suggest that in the pig ET-1 is a more potent constrictor of vascular than of bronchial smooth muscle. The vasoconstrictor activity was greater in the pulmonary than the sys temic circulations.