H. Asano et al., PROSTAGLANDIN H-2 AS AN ENDOTHELIUM-DERIVED CONTRACTING FACTOR MODULATES ENDOTHELIN-1-INDUCED CONTRACTION, Journal of hypertension, 12(4), 1994, pp. 383-390
Objective: To investigate the possible involvement of prostaglandin H-
2, an endothelium-derived contracting factor. in the rat aorta, in the
development of the contraction induced by endothelin-1. Methods: The
aortic rings from spontaneously hypertensive rats (SHR) were prepared,
and the changes of isometric tension of these rings developed by endo
thelin-1 were recorded with or without the treatment of several inhibi
tors or an antagonist. The concentrations of prostaglandins and thromb
oxane B-2 in the bath solution with the rings contracted by endothelin
-1 were measured by radioimmunoassay. The effects of a thromboxane A(2
)/prostaglandin H-2 receptor antagonist (ON0-3708) on endothelin-1-ind
uced contraction were compared in SHR and Wistar-Kyoto (WKY) rats. Res
ults: Indomethacin (10(-5) mol/l) and ONO-3708 (10(-6) mol/l) signific
antly diminished endothelin-1 (3 x 10(-8) mol/l)-induced contractions
in the aortic rings from SHR with but not without endothelium. The thr
omboxane A(2) synthetase inhibitors OKY-046 (10(-5) mol/l) and RS-5186
(10(-5) mol/l) did not attenuate the contractions either with or with
out endothelium. Endothelin-1 significantly increased the release of 6
-keto-prostaglandin F-1 alpha, which is the metabolite of prostaglandi
n I-2 and its precursor prostaglandin H-2, from rings with endothelium
of SHR, but the concentration of thromboxane B-2 from aortic rings wa
s unchanged. In the rings without endothelium the endothelin-1-induced
release of 6-keto-prostaglandin F-1 alpha was also observed. The half
-maximal effective concentration of endothelin-1 for rings from SHR wa
s shifted to the right by ONO-3708, but that of WKY rats was not chang
ed, and significantly greater amounts of 6-keto-prostaglandin F-1 alph
a were released in the rings from SHR than in those from WKY rats by e
ndothelin-1. Conclusions: Endothelin-1 induced the release of prostagl
andin H-2 from endothelial cells in the rat aorta, the effect being gr
eater in the hypertensive state. The released prostaglandin H-2, an en
dothelium-derived contracting factor, modulated the vasoconstriction t
hat is induced by endothelin-1, another endothelium-derived contractin
g factor, in addition to the direct vasoconstrictive action of endothe
lin-1 on vascular smooth muscle.