Role of eicosanoids in rat aortic ring response to agonists and acetylcholine with special reference to the biphasic effects of prostacyclin.
To examine the role of prostanoid release during vascular contraction and endothelium-dependent relaxation, isolated rat thoracic aortic rings were contracted with norepinephrine (NE) or the thromboxane analog U46,619 and then exposed to acetylcholine (ACh). Pretreatment of aortic rings with the cyclooxygenase inhibitor indomethacin decreased (P < 0.05) NE and U46,619-induced contraction. Subsequent ACh-mediated relaxation was also reduced (P < 0.05) in the indomethacin-treated rings. These observations suggest that cyclooxygenase products participate in the rat aortic contractile response to agonists and the relaxation response to ACh. Since prostacyclin has been claimed to contract rat aortic rings, other sets of aortic rings were precontracted to different preloads with NE and then exposed to varying concentrations to prostacyclin (0.02 to 4000 ng/ml). Prostacyclin in modest amounts uniformly decreased aortic ring tension, while greater (> or = 2000 ng/ml) concentrations resulted in a modest contractile response. Prostacyclin per se had minimal contractile effect on quiescent rat aortic rings, but only at unphysiological concentrations. These observations indicate that the primary effect of prostacyclin on rat aortic rings is vasorelaxation, but very high, unphysiological concentrations may result in contraction.
Yang
B C
BC
Department of Medicine, University of Florida College of Medicine, Gainesville.
Lawson
D N
DN
Mehta
J L
JL
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D011464:Epoprostenol; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin