Endothelium-dependent relaxation of rabbit aorta. I. Relaxation stimulated by arachidonic acid.
Vascular responses to the addition of arachidonic acid (AA) were characterized in rings of rabbit thoracic aorta. In preparations which were precontracted to a stable plateau by 10(-7) M phenylephrine, AA (10-100 microM) elicited transient relaxation if the endothelium was intact. The same concentrations of AA only contracted tissues in which the endothelium was purposely disrupted. Indomethacin pretreatment (14 microM, 30 min) potentiated the relaxation response in intact rings. Under these conditions, relaxation in response to 100 microM AA was 32(+/- 3)% of the tension stimulated by 10(-7) M phenylephrine. Preincubation with 5,8,11,14-eicosatetraynoic acid (50 microM) or nordihydroguaiaretic acid (25 microM) completely prevented AA-induced relaxation. Contractile responses to AA were examined in rings lacking pre-existing active tension. AA (3-100 microM) elicited rapidly developing and somewhat transient contractions in rings with endothelium. Slow developing contractions which were significantly smaller in magnitude were observed in rings lacking endothelium. Indomethacin or 5,8,11,14-eicosatetraynoic acid pretreatment inhibited AA-stimulated contractions both in intact and de-endothelialized tissues. Nordihydroguaiaretic acid pretreatment had no effect on contractile responses in rings lacking endothelium and slightly potentiated responses in intact rings. We conclude that endothelium-dependent relaxation of rabbit aorta by AA is mediated by a noncyclooxygenase metabolite(s). Contractile responses are mediated by cyclooxygenase metabolites, which in intact rings are derived largely from the vascular endothelium.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004727:Endothelium / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011817:Rabbits
D001095:Arachidonic Acids; D002396:Catechols; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D009637:Masoprocol; D007213:Indomethacin