Role of neuronal and vascular Ca(2+)-channels in the ACTH-induced reversal of haemorrhagic shock

Br J Pharmacol. 1993 Jul;109(3):645-50. doi: 10.1111/j.1476-5381.1993.tb13621.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / antagonists & inhibitors
  • Adrenocorticotropic Hormone / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Injections, Intravenous
  • Injections, Intraventricular
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Neurons / drug effects*
  • Nicardipine / pharmacology
  • Peptides / pharmacology
  • Rats
  • Rats, Wistar
  • Respiration / drug effects
  • Shock, Hemorrhagic / physiopathology*
  • omega-Conotoxin GVIA

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Peptides
  • Adrenocorticotropic Hormone
  • omega-Conotoxin GVIA
  • Nicardipine