Inhibition of nitric oxide synthases enhances the effect of ACTH in hemorrhagic shock.
In a model of volume-controlled hemorrhagic shock in rats, invariably leading to death within 30 min of bleeding termination, the intravenous (i.v.) bolus injection of ACTH-(1-24) at the dose of 0.16 mg/kg restored cardiovascular and respiratory functions and greatly prolonged survival. I.v. or intracerebroventricular (i.c.v.) treatment with NG-nitro-L-arginine methylester (L-NAME), a non-isoform-selective inhibitor of nitric oxide synthases (NOSs), at the doses of 2.5-10 mg/kg i.v. or 0.015-0.135 mg/kg i.c.v., as well as i.v. treatment with S-methylisothiourea (SMT), a selective inhibitor of the inducible isoform of NOS, at the doses of 0.001-3 mg/kg, dose-dependently improved cardiovascular and respiratory functions and potentiated the effect of a subthreshold dose (0.02 mg/kg) of ACTH-(1-24). On the other hand, either intraperitoneal or i.c.v. pretreatment with L-arginine, the substrate of NOSs, prevented the effect of ACTH-(1-24). These data suggest that inhibition of NO overproduction is involved in the mechanism of action of ACTH-(1-24) in shock reversal.
Bazzani
C
C
Department of Biomedical Sciences, University of Modena, Italy.
Bertolini
A
A
Guarini
S
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003366:Cosyntropin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000201:enzymology*
D004791:Enzyme Inhibitors; D003366:Cosyntropin; D007550:Isothiuronium; D001120:Arginine; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium; D019331:NG-Nitroarginine Methyl Ester