Circulatory effects of endothelin in newborn piglets

Endothelin, a recently described endothelial cell-derived peptide, produces pulmonary and coronary vasoconstriction in mature animals. We investigated the acute hemodynamic effects of porcine endothelin in 14 anesthetized open-chest newborn piglets during normoxia (Pa(O2) = 102 ± 5 mmHg) and hypoxia (fractional inspired O₂ concentration = 0.12 X 15 min, Pa(O2) = 31 ± 1 mmHg). Six of these animals were pretreated with indomethacin, a cyclooxygenase inhibitor. Low-dose (100 pmol/kg) intravenous bolus injection of endothelin decreased pulmonary vascular resistance index (PVRI) (42 ± 6 to 16 ± 4 mmHg·l^-1·min·kg, P < 0.01) and increased coronary blood flow (CBF) (17 ± 2%, P < 0.01); cardiac index (CI) and coronary vascular resistance were unaffected. The pulmonary and coronary responses to endothelin were preserved during hypoxia: PVRI fell (160 ± 22 to 83 ± 13 mmHg·l^-1·min·kg, P < 0.05) and CBF rose (35 ± 11%, P < 0.05). Low-dose endothelin moderately increased mean arterial pressure (61 ± 3 to 75 ± 6 mmHg, P < 0.05) and systemic vascular resistance index (SVRI) (375 ± 23 to 491 ± 41 mmHg·l^-1·min·kg, P < 0.01). High-dose (1,000 pmol/kg) endothelin mildly decreased PVRI (51 ± 7 to 35 ± 12, NS), moderately increased SVRI (375 ± 45 to 594 ± 95 mmHg·l^-1·min·kg, P < 0.05), and markedly diminished CBF (-54 ± 6%, P < 0.01). Left ventricular end-diastolic pressure rose (9 ± 1 to 17 ± 3 mmHg, P < 0.05) and shortening fraction fell (15.9 ± 1.4 to 11.1 ± 2.0%, P < 0.05) in response to high-dose endothelin. CI did not change. Pretreatment with indomethacin did not significantly alter either the pulmonary or coronary vascular responses to low-dose endothelin but completely prevented high-dose endothelin-induced coronary vasoconstriction and left ventricular dysfunction. The results indicate that cyclooxygenase products are unlikely to exclusively mediate endothelin-induced vasodilation but may play a role in endothelin-induced coronary vasoconstriction in newborn piglets.