Role of neuronal and vascular Ca(2+)-channels in the ACTH-induced reversal of haemorrhagic shock.
1. In a rat model of volume-controlled haemorrhagic shock causing the death of all control (saline-treated) animals within 30 min, the intravenous (i.v.) bolus injection of ACTH-(1-24) at a dose of 160 micrograms kg-1 produced an impressive and sustained restoration of arterial pressure, pulse pressure and respiratory function, with 100% survival at the end of the observation period (2 h). 2. Both intracerebroventricular (i.c.v., 0.015-0.06 microgram kg-1) and i.v. (5 micrograms kg-1) pretreatment with the N-calcium channel blocker, omega-conotoxin GVIA, and i.v. (but not i.c.v.) pretreatment with the L-calcium channel blocker, nicardipine (125-500 micrograms kg-1) dose-dependently prevented the ACTH-induced shock reversal. 3. These results further indicate that the effect of ACTH in haemorrhagic shock may involve a neuronal link and the eventual restoration of vascular tone mediated by N- and L-type calcium channels, respectively.
Institute of Pharmacology, University of Modena, Italy.
S
S
Guarini
C
C
Bazzani
A
A
Bertolini
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D000324:Adrenocorticotropic Hormone; D020866:omega-Conotoxin GVIA; D009529:Nicardipine