AJP - Heart and Circulatory Physiology, Vol 258, Issue 5 1449-H1456, Copyright © 1990 by American Physiological Society
Release of EDRF from canine renal artery by leukotriene D4
J. R. Pawloski and B. M. Chapnick
Department of Pharmacology, St. Louis University School of Medicine, Missouri 63104.
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.
