Vascular smooth muscle contractile function is impaired during early and late stages of sepsis.
Although impairment of vascular smooth muscle contractility occurs during the late stages of polymicrobial sepsis, it is not known whether this also occurs in early stages of sepsis and, if so, whether different mechanisms are responsible for such smooth muscle dysfunction. To determine this, rats were subjected to sepsis by cecal ligation and puncture (CLP). Immediately following CLP or sham operation, all animals received 3 ml/100 g body wt normal saline. Septic and sham rats were then sacrificed at 5, 10, or 35 hr after CLP (5-10 hr post-CLP, early sepsis; 35 hr post-CLP, late sepsis), and aortic rings were prepared for contraction studies using organ chamber technique. Dose-response contractions to norepinephrine (NE, 10(-9) to 10(-5) M; receptor-mediated process) and KCl (7.5 to 90 mM; non-receptor mediated) were determined in rings with or without intact endothelium. Endothelial cell removal was confirmed by the absence of relaxation in response to an endothelium-dependent vasodilator, acetylcholine. The results indicate that NE- and KCl-induced vascular contractions were not altered at 5 hr after CLP. At 10 hr post-CLP, however, vascular contractility decreased markedly in the endothelium intact rings. Endothelium removal at 10 hr after CLP restored the contraction induced by NE and KCl to sham levels. In contrast, the smooth muscle contractile dysfunction, observed during late sepsis (35 hr post-CLP), was not restored by the removal of endothelium. Thus, the smooth muscle impairment, observed in early sepsis, is due to mediators released from septic endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, Michigan State University, East Lansing 48824.
S H
SH
Wurster
P
P
Wang
R E
RE
Dean
I H
IH
Chaudry
D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology; D001424:Bacterial Infections / Q000503:physiopathology*; D002432:Cecum; D004730:Endothelium, Vascular / Q000503:physiopathology; D066298:In Vitro Techniques; D008026:Ligation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D011189:Potassium Chloride; D009638:Norepinephrine