Comparative study of the circulatory effects of aminoguanidine and N-nitro-L-arginine in hyperdynamic endotoxemia.
We have studied the effects of NG-nitro-L-arginine (NNA) a nitric oxide synthase (NOS) inhibitor, and aminoguanidine (AG) a diamine oxidase inhibitor, on hemodynamic parameters and plasma histamine level using a dog model in which a hyperdynamic circulatory response was elicited with a 2-hour infusion of a low dose (13.75 micrograms/kg) of E. coli 055:B5 endotoxin (ETX). AG (50 mg/kg) or NNA (0.5 mg/kg) was administered intravenously as pretreatment. Hemodynamic variables were studied for 4 hours after the beginning of the ETX infusion. The ETX-elicited hyperdynamic response was abolished by NNA and partially inhibited by AG. AG prevented the increases in cardiac output and heart rate and delayed the early decrease in total peripheral resistance (TPR). The plasma histamine concentration elevation was higher in animals receiving AG than in those receiving only ETX. In the group treated with ETX plus NNA the cardiac output was lower and the TPR was higher than in the ETX plus AG group. In future studies, AG should be considered as one of the possible therapeutic tools in sepsis, as its adverse effect on the compensatory hyperdynamic response is less than that of NOS inhibitors of the L-arginine analog type, while it may favourably influence the deleterious excessive activity of the inducible NOS in the later stages.
Tárnoky
K
K
Institute of Experimental Surgery, Szent-Györgyi Albert Medical University, Szeged, Hungary.
Kaszaki
J
J
Szalay
L
L
Boros
M
M
Nagy
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D019446:Endotoxemia / Q000503:physiopathology*; D004731:Endotoxins; D004926:Escherichia coli; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000097:blood; D006636:Histamine Release / Q000187:drug effects; D019335:Nitroarginine / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D004731:Endotoxins; D006146:Guanidines; D019335:Nitroarginine; D006632:Histamine; C004479:pimagedine