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Activities of endothelin‐1 in the vascular network of the rabbit ear: a microangiographic study
Author(s) -
Randall Michael D.,
Edwards David H.,
Griffith Tudor M.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14157.x
Subject(s) - potency , constriction , endothelin receptor , perfusion , endothelin 1 , vasodilation , endocrinology , medicine , endothelium , hypoxia (environmental) , vasoconstriction , endothelium derived relaxing factor , contraction (grammar) , blood vessel , circulatory system , endothelins , chemistry , receptor , in vitro , biochemistry , oxygen , organic chemistry
1 The effects of endothelin‐1 on perfusion pressure and on arterial and venous diameters were examined simultaneously in a rabbit isolated ear preparation perfused with physiological buffer. The effects of hypoxia and inhibition of endothelium‐derived relaxant factor (EDRF) activity on vascular responses to endothelin‐1 were also investigated. 2 Endothelin‐1 was potent at increasing perfusion pressure (ED 50 = 46.7 ± 11.0 pmol; R max = 85.3 ± 5.3 mmHg). The potency and maximum reactivity were not significantly affected by hypoxia, inhibition of EDRF activity with 50 μ m N‐nitro‐ l ‐arginine methyl ester (NAME) or a combination of hypoxia and NAME. 3 Endothelin‐1 caused equipotent dose‐dependent constrictions of the first four generations of arterial branch vessels (G 1 ‐G 4 ) but did not influence the diameter of the central ear artery except at high doses of the peptide when ‘paradoxical dilatation’ was observed. The peptide was also equipotent at causing constriction of the smaller venous vessels (V 1 ‐V 4 ) but did not affect the large veins (V 0 ). 4 Under conditions of hypoxia the potency of endothelin‐1 was reduced in G 2 and G 3 , was unaffected in G 4 and the peptide did not significantly constrict either G 0 or G 1 . Hypoxia reduced the potency of endothelin‐1 in the smaller venous vessels (V 1 ‐V 4 ), but conversely unmasked a marked constriction of the large veins (V 0 ), which was not observed under normoxic conditions. 5 NAME 50 μ m abolished the vasodilator effects of acetylcholine in this preparation. Inhibition of EDRF activity with NAME under normoxic conditions did not influence the constrictor activity of endothelin‐1 on the arterial or venous branch vessels. However, inhibition of EDRF activity under hypoxic conditions prevented the reduction of potency of endothelin‐1 as a constrictor of arterial and venous branch vessels which occurred in hypoxia. In the presence of NAME endothelin‐1 constricted V 0 in both normoxia and hypoxia with equipotency but the maximum effect was greatest in hypoxia. 6 In conclusion, endothelin‐1 is a powerful vasoconstrictor which acts with greater potency in veins than arteries in the rabbit isolated ear. Although hypoxia does not influence pressor responses it nevertheless alters the spatial pattern of vasoconstriction. In particular hypoxia unmasks constriction of the large veins by endothelin‐1. Constriction of these veins was also observed in the absence of EDRF in normoxia, but to a much lesser degree so that the effect of hypoxia may only be partially due to reduced EDRF activity. Hypoxia may therefore directly or indirectly increase the sensitivity of the main veins to endothelin‐1.