Cyclooxygenase inhibitors attenuate endothelin ET(B) receptor-mediated contraction in human temporal artery.
It is well documented that endothelin ET(B) receptor-mediated contraction develops in artery segments incubated in culture and that the reaction is augmented by proinflammatory cytokines, but little is known of the mechanisms involved. Segments of human temporal artery were incubated in organ culture for 2 days in the absence or presence of interleukin-1 beta (IL-1 beta), with or without nonsteroidal anti-inflammatory drugs, glucocorticoids or a nitric oxide synthase inhibitor. Thereafter, contractions were induced by the selective endothelin ET(B) receptor agonist, sarafotoxin S6c. Acetylsalicylic acid, indomethacin, nimesulide and rofecoxib were all effective in eliminating the increase in endothelin ET(B) receptor-mediated contraction induced by interleukin-1 beta, but only indomethacin and rofecoxib significantly reduced the spontaneous development of this reaction in cultured arteries. Dexamethasone and methylprednisolone augmented the reaction, and the nitric oxide synthase inhibitor had no effect. The results clearly indicate a role for cyclooxygenase, most likely cyclooxygenase-2, in endothelin ET(B) receptor-mediated contraction in this preparation.
Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, N-7006 Trondheim, Norway. Linda.White@medisin.ntnu.no
Linda R
LR
White
Roar
R
Juul
Johan
J
Cappelen
Jan
J
Aasly
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009924:Organ Culture Techniques; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects*; D013699:Temporal Arteries / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin