INVITRO RESPONSES OF OVINE INTRAPULMONARY ARTERIES AND VEINS TO ENDOTHELIN-1

We determined responses of third-generation intrapulmonary arteries and veins of fetal, newborn, and adult sheep to endothelin-1 (ET) and the role of endothelium and cyclooxygenase metabolites in ET effects in adult sheep lung vessels. Presence of endothelium in vessel rings was confirmed by response to endothelium-dependent vasodilators, acetylcholine or bradykinin. Vessel tension induced by ET was expressed as a percentage of tension induced by 100 mM KCl. We found that arteries and veins contracted to 10(-9) to 10(-6) M ET in a dose-dependent manner. Veins exhibited greater sensitivity to ET than arteries in all age groups. Arteries and veins of adult sheep lungs were more sensitive to ET than those of fetal and newborn lambs. In adult sheep lung vessels, pretreatment with indomethacin 5 x 10(-6) M) and SQ 29548, a thromboxane A2-prostaglandin H-2 receptor antagonist (10(-5) M), significantly attenuated venous contraction to ET; arterial contraction was unaffected. Denuding vessels of endothelium did not affect responses to ET. We conclude that, in ovine lungs, veins are more sensitive to ET than arteries and that developmental differences in pulmonary vascular responses to ET exist.