Time course of liver nitric oxide concentration in early septic shock by cecal ligation and puncture in rats.
An overwhelming nitric oxide (NO) production is a crucial step in the circulatory events as well as in the cellular alterations taking place in septic shock. However, evidences of this role arise from studies assessing the NO production on an intermittent basis precluding any clear evaluation of temporal relationship between NO production and circulatory alterations. We evaluated this relationship by using a NO specific electrode allowing a continuous measurement of NO production. Septic shock was induced by a cecal ligation and puncture (CLP) in a first group of anesthetized rats. After the same CLP, a second group received a selective iNOS inhibitor (L-NIL). Control rats were sham operated or sham operated with L-NIL administration. While NO concentration was measured every 2 min by a NO-sensitive electrode over 7h following CLP, the liver microcirculation was recorded by a laser-Doppler flowmeter. CLP induced a severe septic shock with hypotension occurring at a mean time of 240 min after CLP. At the same time, an increase in liver NO concentration was observed, whereas a decrease in microvascular liver perfusion was noted. In the septic shock group, L-NIL administration induced an increase in arterial pressure whereas the liver NO concentration returned to baseline values. In addition, shock groups experienced an increase in iNOS mRNA. These data showed a close temporal relationship between the increase in liver NO concentration and the microvascular alteration taking place in the early period of septic shock induced by CLP. The iNOS isoform is involved in this NO increase.
Eyenga
P
P
Inserm, EA4173 ERI 22, Agression vasculaire et réponses tissulaires, UCBLyon1, 69008 Lyon, France.
Lhuillier
F
F
Morel
J
J
Roussel
D
D
Sibille
B
B
Letexier
D
D
Cespuglio
R
R
Duchamp
C
C
Goudable
J
J
Bricca
G
G
Viale
J P
JP
D000818:Animals; D002432:Cecum / Q000601:surgery*; D004195:Disease Models, Animal; D004566:Electrodes; D008026:Ligation; D008099:Liver / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis* / Q000096:biosynthesis; D010538:Peritonitis / Q000503:physiopathology; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000503:physiopathology*; D013997:Time Factors
D009569:Nitric Oxide