Attenuation of corticotropin releasing factor-induced hypotension in anesthetized rats with the CRF antagonist, alpha-helical CRF9-41; comparison with effect on ACTH release.

Abstract

The effect of pretreatment with the corticotropin releasing factor (CRF-41) antagonist, alpha-helical CRF(9-41), on the hypotensive response obtained on peripheral administration of CRF-41 has been assessed in anesthetized Wistar rats. A single IV bolus dose of rat CRF-41 (2 nmol, at 0 min) produced a hypotensive effect which was rapid in onset (-52 mmHg at +1 min) and sustained throughout the 60-min study period (-42, -40, -26 and -16 mmHg at +3, +10, +30 and +60 min, respectively). The antagonist [alpha CRF(9-41)] was administered in consecutive bolus doses of 12.5, 25 and 50 nmol at -15, -10 and -5 min, respectively. This had no effect on mean arterial blood pressure (MABP) or heart rate, nor did it change significantly the magnitude of the initial rapid fall in MABP when CRF-41 was administered (-45 mmHg at +1 min). However, following pretreatment with alpha CRF(9-41), MABP returned to control values within 3 min and the sustained period of hypotension was completely blocked. Administration of CRF-41 resulted in 44% and 142% increases in norepinephrine and epinephrine measured at +60 min. Pretreatment with the antagonist attenuated the rise in circulating catecholamine levels observed after CRF-41 administration. In comparison, pretreatment with the antagonist did not alter the ACTH response to CRF-41 at +1 and +3 min and only reduced ACTH levels by 28% (p less than 0.05), 43% (p less than 0.001) and 41% (p less than 0.01) at 10, 30 and 60 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: R Corder, D Turnill, N Ling, R C Gaillard
• Journal: Peptides (Peptides) 1992 Jan-Feb Vol. 13 Issue 1 Pg. 1-6 ISSN: 0196-9781 [Print] United States
• PMID: 1320258 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catecholamines
• Neuropeptide Y
• Peptide Fragments
• Adrenocorticotropic Hormone
• Corticotropin-Releasing Hormone
• corticotropin releasing hormone (9-41)

Topics

• Adrenocorticotropic Hormone (drug effects, metabolism)
• Anesthesia, Intravenous
• Animals
• Blood Pressure Determination
• Catecholamines (blood)
• Cells, Cultured
• Corticotropin-Releasing Hormone (antagonists & inhibitors, pharmacology)
• Female
• Hypotension (metabolism)
• Neuropeptide Y (blood)
• Peptide Fragments (pharmacology)
• Pituitary Gland, Anterior (cytology, metabolism)
• Protein Conformation
• Rats