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Flushing and haemodynamic responses to vasopressin peptides in the rhesus monkey
Author(s) -
Brooks David P.,
Koster Paul F.,
Stassen Frans L.,
Albrightson Christine R.,
Huffman William F.,
Wasserman Martin A.,
Kinter Lewis B.
Publication year - 1988
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.1476-5381.1988.tb11586.x
Subject(s) - vasopressin , tachycardia , medicine , endocrinology , flushing , antagonist , mast cell , agonist , anesthesia , receptor , immunology
1 The mechanism of the flushing, hypotension and tachycardia associated with i.v. administration of desGlyd(CH 2 ) 5 D‐Tyr(Et)VAVP (SK&F 101926; 25 μg kg −1 ) and the selective V 2 antidiuretic agonist, desamino‐8‐D‐arginine vasopressin (dDAVP; 3 μg kg −1 ) was studied in ketamine‐anaesthetized rhesus monkeys. 2 The flushing associated with SK&F 101926 was reduced by pretreatment with a mast cell stabilizer and by repeated administration of peptide (within 2–4 weeks). A similar desensitization to dDAVP‐associated flushing was observed on repeated administration. 3 Treatment with dDAVP also resulted in reduced SK&F 101926‐associated flushing. 4 The hypotension associated with SK&F 101926 was not affected by pretreatment with a mast cell stabilizer. A similar degree of hypotension was observed with repeated administration of either SK&F 101926 or dDAVP. 5 The tachycardia associated with SK&F 101926 was reduced by pretreatment with a mast cell stabilizer or repeated administration of SK&F 101926. Repeated administration of dDAVP, however, resulted in an enhanced tachycardia. 6 Indomethacin (5 mg kg −1 i.v.) did not alter the flushing or the hypotension associated with the administration of either SK&F 101926 or dDAVP, but resulted in an enhanced tachycardia to SK&F 101926. 7 Administration of a selective V 1 vasopressor antagonist did not result in flushing, hypotension or tachycardia. 8 It was concluded that the flushing response to vasopressin‐like peptides in rhesus monkeys may be due to an action on mast cells, whereas the haemodynamic responses are not, but probably involve direct vasodilator actions.