Attenuation of corticotropin releasing factor-induced hypotension in anesthetized rats with the CRF antagonist, alpha-helical CRF9-41; comparison with effect on ACTH release.
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)
Corder
R
R
Department of Medicine, University Hospital, Geneva, Switzerland.
Turnill
D
D
Ling
N
N
Gaillard
R C
RC
D000324:Adrenocorticotropic Hormone / Q000187:drug effects / Q000378:metabolism*; D000771:Anesthesia, Intravenous; D000818:Animals; D001795:Blood Pressure Determination; D002395:Catecholamines / Q000097:blood; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D005260:Female; D007022:Hypotension / Q000378:metabolism*; D009478:Neuropeptide Y / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats
D002395:Catecholamines; D009478:Neuropeptide Y; D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)