Effects of nitric oxide synthase inhibition on the hemodynamic changes in hyperdynamic endotoxemia.
In this study we compared the circulatory effects of the arginine analogue non-specific nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine (NNA), and the specific inducible NOS (iNOS) inhibitor S-methylisothiourea (SMT) and S-(2-aminoethyl)-isothiourea (AEST) in a hyperdynamic endotoxemic dog model. Mean arterial pressure (MAP), cardiac output (CO), and myocardial contractility (MC) were measured. A hyperdynamic circulatory response was elicited with a 2-h infusion of a total dose of 5.3 micrograms/kg E. coli endotoxin (ETX). NOS inhibitory treatment (2 mg/kg) was administrated from the 45th min of endotoxemia. ETX induced a hyperdynamic circulatory response, and a significant myocardial depression. NNA induced a prolonged, SMT a transient increase in MC, both drugs elevated MAP, but decreased CO. AEST significantly prolonged the elevation in CO, but did not affect MAP. Selective inhibition of the iNOS may be a beneficial in sepsis.
Wolfárd
A
A
Institute of Experimental Surgery, Szent-Györgyi Albert Medical University, Szeged, Hungary.
Kaszaki
J
J
Szabó
C
C
Balogh
Z
Z
Nagy
S
S
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D019446:Endotoxemia / Q000188:drug therapy / Q000503:physiopathology*; D004731:Endotoxins / Q000008:administration & dosage / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology*
D004731:Endotoxins; D004791:Enzyme Inhibitors; D000338:beta-Aminoethyl Isothiourea; D019335:Nitroarginine; D007550:Isothiuronium; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium