Endothelium-dependent microvascular responses to activated complement.
Infusion of Escherichia coli bacteria to cause high cardiac output bacteremia produces a differential microvascular response with constriction of large arterioles and dilation of small arterioles in skeletal muscle of rats. An important component to host-defense mechanisms during bacteremia is activation of the complement system. One part of this study explored the possibility that microvascular responses to bacteremia could be mediated by activation of the alternative complement cascade to alter skeletal muscle blood flow during sepsis. Complement activation by iv zymosan into unanesthetized (decerebrate) Sprague-Dawley rats caused constriction of large arterioles and dilation of small arterioles in cremaster muscle, while cardiac output stayed normal or was elevated. These microvascular responses mimic those during bacteremia, suggesting that components of the complement system mediate skeletal muscle microcirculatory responses to live E. coli sepsis. The vasodilation response of small arterioles in skeletal muscle during bacteremia is endothelium-dependent and is mediated at least partially by endothelial-derived relaxing factor (EDRF). Complement activation gives products which interact with endothelial cells. Thus, a second part of this study explored the role of EDRF in the vasodilation of skeletal muscle small arterioles during activation of the alternate complement pathway. Blockade of EDRF action by hydroquinone totally abolished small arteriole dilation and large arteriole constriction responses to complement activation by zymosan infusion.
Lübbe
A S
AS
Department of Medicine, R. Virchow Medical School, Freie Universität Berlin, Federal Republic of Germany.
Garrison
R N
RN
Harris
P D
PD
D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology*; D003165:Complement System Proteins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004927:Escherichia coli Infections / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006873:Hydroquinones / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D015054:Zymosan / Q000494:pharmacology
D006873:Hydroquinones; D009569:Nitric Oxide; D003165:Complement System Proteins; D015054:Zymosan; C031927:hydroquinone