Flushing and haemodynamic responses to vasopressin peptides in the rhesus monkey.

1. The mechanism of the flushing, hypotension and tachycardia associated with i.v. administration of desGlyd(CH2)5D-Tyr(Et)VAVP (SK&F 101926; 25 micrograms kg-1) and the selective V2 antidiuretic agonist, desamino-8-D-arginine vasopressin (dDAVP; 3 micrograms 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 V1 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.
AuthorsD P Brooks, P F Koster, F L Stassen, C R Albrightson, W F Huffman, M A Wasserman, L B Kinter
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 94 Issue 3 Pg. 759-64 (Jul 1988) ISSN: 0007-1188 [Print] ENGLAND
PMID3179611 (Publication Type: Journal Article)
Chemical References
  • Arginine Vasopressin
  • 1-((beta-mercapto-beta)beta cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-9-des-Gly-arginine vasopressin
  • Deamino Arginine Vasopressin
  • Indomethacin
  • Animals
  • Arginine Vasopressin (analogs & derivatives, pharmacology)
  • Blood Pressure (drug effects)
  • Deamino Arginine Vasopressin (pharmacology)
  • Disease Models, Animal
  • Flushing (chemically induced, prevention & control)
  • Heart Rate (drug effects)
  • Hemodynamics (drug effects)
  • Indomethacin (pharmacology)
  • Macaca mulatta
  • Male

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