Effect of ACTH-(4-10) and gamma 2-MSH on blood pressure after intracerebroventricular and intracisternal administration.

After intracerebroventricular (i.c.v.) administration of ACTH-(4-10) or gamma 2-MSH in doses of < or = 1,500 pmol, no changes were observed in mean arterial pressure (MAP) of conscious and urethane-anesthetized rats. When gamma 2-MSH was administered intracisternally (i.c.), a significant increase in MAP of approximately 15 mm Hg was observed after the two highest doses used (500 and 1,500 pmol) in conscious rats and also, though less pronounced, in urethane-anesthetized rats. Although the pressor effect of gamma 2-MSH after intravenous (i.v.) administration to conscious rats was maximal within 25 s and MAP had returned to preinjection values < or = 60 s, the pressor response after i.c. administration was slower in onset (maximal effect after 1-2 min) and of longer duration (return to preadministration values after 5 min). ACTH-(4-10) had a slight pressor effect after i.c. administration in doses of 1,500 and 2,500 pmol in conscious rats, but had no effect in urethane-anesthetized rats. These results indicate that sustained leakage of the peptides after i.c. administration, but not after i.c.v. administration, to the periphery is the causal factor of a modest pressor response. These results do not support the suggestion that the central nervous system (CNS) is the principal target of gamma-MSH-like peptides with respect to their pressor effect.