ENDOTHELIUM DEPENDENCY OF CONTRACTILE ACTIVITY DIFFERS IN INFANT AND ADULT VERTEBRAL ARTERIES

Contractions to serotonin (5-HT) and endothelin-1 (ET-1) in infant (0- 2 yr) and adult (38-71 yr) vertebral arteries were examined in the pre sence of either the cyclooxygenase inhibitor indomethacin or N-G-monom ethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide production. In addition, endothelium-dependent relaxations to acetylcholine were cha racterized in arteries contracted with agonist. The results showed tha t: (a) Contractions of infant arteries to 5-HT or ET-1 decreased to 44 +/-8% and 27+/-13%, respectively, within 10 min. Indomethacin or remov al of endothelium abolished this decreased response, whereas L-NMMA ha d no effect. (b) Adult arteries produced sustained contractions to 5-H T or ET-1 that were unaffected by indomethacin, endothelium denudation , or L-NMMA. (c) Endothelium-dependent relaxations to acetylcholine we re greater in infant than adult arteries and were abolished by indomet hacin (but not L-NMMA) in infants and L-NMMA (but not indomethacin) in adults. Thus, endothelium-dependent responses in infant arteries are attenuated because of increased prostaglandin activity not observed in adult tissues. Additionally, there is an age-dependent change in the primary mechanism responsible for acetylcholine-induced vasodilatation . Apparently, endothelium dependency of acetylcholine-induced relaxati on is highly dependent on cyclooxygenase activity in the infant verteb ral artery, but in the adult artery, nitric oxide is linked to the vas odilator response.