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Mediation via different receptors of the vasoconstrictor effects of endothelins and sarafotoxins in the systemic circulation and renal vasculature of the anaesthetized rat
Author(s) -
Cristol JeanPaul,
Warner Timothy D.,
Thiemermann Christoph,
Vane John R.
Publication year - 1993
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.1476-5381.1993.tb12877.x
Subject(s) - endothelins , endothelin receptor , vasoconstriction , renal circulation , medicine , endocrinology , vasoconstrictor agents , receptor , kidney , renal blood flow , endothelin 1 , blood pressure , receptor antagonist , antagonist , chemistry , pharmacology
1 Using endothelin‐1 (ET‐1), endothelin‐3 (ET‐3), sarafotoxin 6b (SX6b) and sarafotoxin 6c (SX6c) as agonists and BQ‐123 as a selective ET A receptor antagonist, we have examined the endothelin receptor subtypes mediating the systemic pressor and renal vasoconstrictor effects of the ET/SX family of peptides. 2 In anaesthetized rats, bolus intravenous injections of ET‐1, ET‐3, SX6b or SX6c (0.1, 0.25 and 0.50 nmol kg −1 ) produced initial transient depressor responses followed by sustained and dose‐dependent increases in mean arterial pressure (MAP) with the following rank order of potency: SX6b>ET‐1 ≫SX6c>ET‐3. In contrast, in the renal vasculature these peptides caused equipotent dose‐dependent falls in renal blood flow (RBF) (ET‐1 = ET‐3 = SX6b = SX6c). 3 BQ‐123 (1 mg kg −1 , i.v. bolus) significantly reduced the systemic pressor effects of all the peptides but was largely ineffective against the renal vasoconstrictions. 4 These results indicate that although the systemic pressor effects of the ET/SX peptides are mediated via ET A receptors, the vasoconstriction in the kidney in vivo may be mediated predominantly via ET B ‐like receptors. This may be of therapeutic relevance, for an ET A ‐receptor‐selective antagonist could offer only poor protection of the renal circulation from the deleterious effects of endogenously produced members of this peptide family.