Pharmacological heterogeneity of constrictions mediated by
endothelin receptors in rat pulmonary arteries.
Higashi, Tooru, Takeshi Ishizaki, Kazuo Shigemori, Tuguhiko Nakai,
Susumu Miyabo, Takashi Inui, and Takaki Yamamura.
Third Department of Internal Medicine, Fukui Medical School, Fukui,
910-11 and; International Research Laboratories, Ciba-Geigy Japan,
Takarazuka 665, Japan
APStracts 3:0196L, 1996.
The endothelin (ET) receptors mediating rat pulmonary arterial
constrictions were investigated. ET-1 and ET-3 constricted both
isolated intrapulmonary artery (IPA) and extrapulmonary artery (EPA),
with ET-1 having a potency about 10 times that of ET-3. The ETB
-selective agonist IRL 1620 produced constriction of only IPA. The ETB
selective antagonist BQ788 suppressed the ET-1-induced constriction
of only IPA. The ETA-selective antagonist BQ123 more effectively
antagonized the ET-1-induced constriction of EPA than that of IPA.
The combination of BQ123 and BQ788 increased the antagonistic
response to ET-1 in IPA but not in EPA, then large constriction
remained in IPA and EPA. The receptor non-selective antagonist PD
145065 almost completely inhibited the ET-1-induced constriction of
IPA and EPA. BQ123 completely inhibited the ET-3-induced constriction
of EPA, however it partially suppressed that of IPA. The combination
of BQ123 and BQ788 completely inhibited the ET-3-induced constriction
of IPA. These results demonstrate that the ET-1-induced constrictions
are mediated by both ETA and ETB in IPA and ETA in EPA, and because
of differences in sensitivity to ET receptor antagonists for ET-1-
and ET-3-induced constrictions, pharmacological heterogeneity of ETA
is suggested. Additionally, endothelial denudation affected the ET-3
-induced constriction of EPA, but not of IPA, and it didn't affect the
response to ET-1. This suggests that the vasodilatory effect of
endothelium on ET-3-induced vasoconstrictions varies depending on
pulmonary vascular regions.
Received 17 August 1995; accepted in final form 16 September
1996.
APS Manuscript Number L261-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996