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Role of ET B receptors in local clearance of endothelin‐1 in rat heart: studies with the antagonists PD 155080 and BQ‐788
Author(s) -
Brunner Friedrich,
Doherty Annette M.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)01103-9
Subject(s) - receptor , endothelin receptor , chemistry , medicine , endothelin 1 , antagonist , endocrinology , constriction , pharmacology , biology , biochemistry
The effects of two endothelin (ET) receptor antagonists, PD 155080 (ET A selective) and BQ‐788 (ET B selective), on cardiac function and ET‐1 release were studied in isolated rat hearts. In normoxic hearts, infusion of PD 155080 (50 nM‐5 μM) reduced coronary resistance, but had no effect on ET‐1 release. Low concentrations of BQ‐788 (2 and 20 nM) had no effect on coronary resistance; high concentrations (0.2 and 2 μM) increased it ∼ 2‐fold; all concentrations increased ET‐1 release (up to 24‐fold). Similar results were obtained in reperfused hearts. Although concentrations of ET‐1 were higher in interstitial fluid than coronary effluent, levels never exceeded the low pg/ml range. These results indicate that (1) ET A receptors mediate coronary constriction, whereas ET B receptors bind and sequester ET‐1, and (2) ET‐1 displaced by ET B antagonist accesses ET A receptors resulting in coronary constriction.