Vasoconstrictions mediated by an endothelium-derived vasoconstricting factor (EDCF).
To enlighten the role of endothelium in the generation of vasospasms we examined vascular tone after reduction of oxygen supply in dependence on endothelial function in isolated vessels (rabbit aorta abdominalis, pig coronary, and pulmonary artery). Therefore, after ligation of all side branches, vessel segments, prepared either with or without endothelium, were cannulated and arranged in two systems (with two segments each) in a serial manner (system I: endothelium-denuded vessel followed by an endothelium-denuded segment) and perfused with Tyrode's solution (constant flow 20 ml/min). Pressure gradient over each segment was continuously measured. Endothelial function was checked by perfusion with 1 mumol/l actetylholine after precontraction with 0.1 mumol/l norepinephrine, thereby inducing an EDRF mediated vasodilation (greater than 70%) indicating normal endothelial function. After 2 h equilibration with Tyrode's solution the preparations of rabbit aorta abdominalis were perfused for 30 min with oxygen-deprived medium (reduction from 95% O2 and 5% CO2 to 95% N2 and 5% CO2) and a marked long lasting (60 min) increase in pressure gradient (indicating vasoconstriction) was observed in those endothelium-denuded vessel segments which were mounted distal to a normal vessel with an intact endothelium. This contraction could be inhibited by pretreatment with either 1 mumol/l dexamethasone. 1 mumol/l indomethacine or 10 mumol/l methylene blue or attenuated by the TXA2-antagonist BM 17133 (5 mumol/l) but not by radical scavengers as superoxid dismutase or by inhibition of the lipoxygenase by nordihydroguaretic acid. From these results it is concluded that endothelium releases a vasoconstricting factor (EDCF) at pO2 values beneath 550 mm Hg. This EDCF seems to depend on phospholipase A2 and cyclooxygenase, but because of the long-lasting effect it is probably no prostanoid itself, especially not TXA2.
Dhein
S
S
Pharmacological Institute, University of Cologne, FRG.
Salameh
A
A
Esser
F
F
Klaus
W
W
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001095:Arachidonic Acids / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D016232:Endothelins; D005609:Free Radicals; D006207:Half-Life; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010101:Oxygen Consumption; D010455:Peptides / Q000378:metabolism / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D001095:Arachidonic Acids; D016232:Endothelins; D005609:Free Radicals; D010455:Peptides; D003907:Dexamethasone; D007213:Indomethacin