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 presence of either the cyclooxygenase inhibitor indomethacin or NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide production. In addition, endothelium-dependent relaxations to acetylcholine were characterized in arteries contracted with agonist. The results showed that: (a) Contractions of infant arteries to 5-HT or ET-1 decreased to 44 +/- 8% and 27 +/- 13%, respectively, within 10 min. Indomethacin or removal of endothelium abolished this decreased response, whereas L-NMMA had no effect. (b) Adult arteries produced sustained contractions to 5-HT or ET-1 that were unaffected by indomethacin, endothelium denudation, or L-NMMA. (c) Endothelium-dependent relaxations to acetylcholine were greater in infant than adult arteries and were abolished by indomethacin (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 vasodilation. Apparently, endothelium dependency of acetylcholine-induced relaxation is highly dependent on cyclooxygenase activity in the infant vertebral artery, but in the adult artery, nitric oxide is linked to the vasodilator response.
Charpie
J R
JR
Department of Pediatric Cardiology, University of Michigan Medical School, Ann Arbor 48109-0622.
Schreur
K D
KD
Papadopoulos
S M
SM
Webb
R C
RC
D000328:Adult; D000367:Age Factors; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002675:Child, Preschool; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction; D014711:Vertebral Artery / Q000502:physiology*; D019323:omega-N-Methylarginine
D016232:Endothelins; D019323:omega-N-Methylarginine; D012701:Serotonin; D001120:Arginine