Low-level expression and limited role for the inducible isoform of nitric oxide synthase in the vascular hyporeactivity and mortality associated with cecal ligation and puncture in the rat.
Expression of the inducible isoform of nitric oxide synthase (iNOS) contributes to the hypotension and vascular hyporeactivity in various models of shock induced by bacterial lipopolysaccharide (LPS). However, the role of iNOS in response to shock caused by live bacteria is more controversial. In the present study, we investigated the role of iNOS in a rat model of cecal ligation and puncture (CLP). CLP resulted in increased plasma nitrite/nitrate levels (up to 59 microM at 24 h) and increased pulmonary iNOS activity (up to 71 fmoles/mg/min at 12 h) and caused a significant vascular hyporeactivity at 18 h. The degree of NO production and iNOS induction was approximately 30% of that observed several hours after administration of LPS in the same species, and the degree of vascular hyporeactivity was less than that observed after LPS injection. Selective inhibition of iNOS with mercaptoethylguanidine (MEG) reduced plasma nitrite/nitrate levels, but did not prevent the development of vascular hyporeactivity, and did not improve survival in this model of CLP. Thus, CLP-induced sepsis causes low-level induction of iNOS, but factors other than iNOS are the crucial determinants of the vascular failure and mortality in this model.
Children's Hospital Medical Center, Department of Pediatric Surgery, Cincinnati, Ohio 45229, USA.
A
A
Vromen
M S
MS
Arkovitz
B
B
Zingarelli
A L
AL
Salzman
V F
VF
Garcia
C
C
Szabó
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002432:Cecum / Q000473:pathology / Q000601:surgery*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007527:Isoenzymes; D008026:Ligation; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000209:etiology* / Q000401:mortality*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*
D004791:Enzyme Inhibitors; D006146:Guanidines; D007527:Isoenzymes; D019001:Nitric Oxide Synthase; C100078:2-mercaptoethylguanidine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine