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)