Release of EDRF from canine renal artery by leukotriene D4.
The goal of the present investigation was to determine whether leukotriene D4 (LTD4) was capable of releasing endothelium-derived relaxing factor (EDRF) from perfused renal arterial (RA) segments and to begin to characterize any released mediator. To detect EDRF, a bioassay was used in which a prostaglandin (PG) F2 alpha precontracted, endothelium-denuded coronary artery (CA) ring was superfused either directly or with effluent from a perfused RA segment. Addition of LTD4 or acetylcholine (ACh) to the perfusate proximal to the RA segment resulted in CA ring relaxation, the degree of which was inversely related to transit time. Calculated half-life (t1/2) for the CA relaxing substance released by LTD4 and ACh from the RA segment was 7.5 +/- 1.4 and 7.4 +/- 0.9 s, respectively. Pretreatment of the RA segment with collagenase prevented relaxation of the CA ring evoked by RA effluent in response to either ACh or LTD4 that was administered into the perfusate proximal to the RA segment. Addition of superoxide dismutase (SOD) to the effluent distal to the RA segment markedly enhanced both ACh and LTD4-evoked relaxation of the CA ring, whereas reduced hemoglobin (Hb) virtually abolished these responses. When either LTD4 or ACh was superfused directly over the CA, no change in tone of the bioassay ring was observed. These data indicate that, similar to ACh, LTD4 has the ability to release a labile substance(s), presumably EDRF, from the endothelium-intact RA segment that evokes relaxation of the endothelium-denuded CA ring. Although apparently similar, further studies are required to confirm whether or not the mediator(s) released by LTD4 is identical to that which is released by ACh.
Pawloski
J R
JR
Department of Pharmacology, St. Louis University School of Medicine, Missouri 63104.
Chapnick
B M
BM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology; D008297:Male; D003012:Microbial Collagenase / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D012077:Renal Artery / Q000378:metabolism*; D013189:SRS-A / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects
D006454:Hemoglobins; D013189:SRS-A; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D003012:Microbial Collagenase; D000109:Acetylcholine