EDRF as a possible mediator of sepsis-induced arteriolar dilation in skeletal muscle.
Vascular endothelial cells influence microvessel diameters in vivo and in vitro and participate in host-defense mechanisms during sepsis. We examined whether small arteriole dilation in skeletal muscle during high cardiac output bacteremia (HOB) and low cardiac output live Escherichia coli sepsis (LOS) is mediated by an endothelium-derived relaxing factor (EDRF). Local chemical blockade of EDRF by hydroquinone (HQ) substantially blunted acetylcholine-induced dilation of small arterioles. HQ also prevented large arteriole (55-135 microns) constriction and small arteriole (6-22 microns) dilation in the cremaster muscle of rats during HOB. In LOS, small arteriole dilation was also prevented by HQ but only during the early period when blood pressure was unchanged from baseline. HQ did not alter large arteriole constriction during LOS. We conclude that small arteriole vasodilation in skeletal muscle is mediated at least in part by EDRF during bacteremia. Because EDRF cannot mediate large arteriole constriction and because HQ blunted large arteriole constriction during HOB, we now suspect that HQ also interferes at least in part with some large arteriole vasoconstrictor mechanism, possibly leukotrienes or an endothelium-derived constricting factor, which mediates large arteriole constriction during HOB. Our data also suggest that large arteriole constriction during LOS is partly mediated by factors that are unaffected by HQ. The endothelium appears to play an important role in the microcirculatory responses of skeletal muscle to live E. coli sepsis through more than one mechanism.
Lübbe
A S
AS
Department of Medicine (Oncology), Freie Universität Berlin, R. Virchow Medical School, Federal Republic of Germany.
Garrison
R N
RN
Cryer
H M
HM
Alsip
N L
NL
Harris
P D
PD
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004927:Escherichia coli Infections / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006873:Hydroquinones / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009132:Muscles / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D006873:Hydroquinones; D009569:Nitric Oxide; D000109:Acetylcholine; C031927:hydroquinone