Adenosine receptor antagonism affects regional resting vascular resistance during rat peritoneal sepsis.
BACKGROUND
To identify vascular beds where endogenous adenosine plays a significant role as a mediator of resting perfusion alterations associated with sepsis, we tested the hypothesis that adenosine receptor blockade would cause differential regional increases in vascular resistance during intraperitoneal (ip) sepsis in the rat.


METHODS
Rats (250-350 g) were catheterized and randomized to septic or nonseptic groups. Sepsis was induced with an ip injection of cecal slurry (150 mg/kg in D5W; 5 ml/kg), and baseline hemodynamics, cardiac output (CO), and blood flows (microspheres) were measured 24 h later. Animals then received the adenosine receptor antagonist 8-phenyltheophylline (8-PTH; 10 mM, 1.5 ml/kg), its vehicle (1.5 ml/kg), or normal saline (1.5 ml/kg), iv, and measurements were repeated.


RESULTS
Septic animals treated with 8-PTH had a significant increase in skeletal muscle, hepatic portal, and cerebral vascular resistance with concomitant decreases in CO when compared with vehicle at 1 min. No significant resistance changes were observed in the renal, adipose, or coronary vasculatures. Adenosine receptor blockade caused a significant increase in +dP/dt and -dP/dt during sepsis, indicating that the reduced CO was not secondary to myocardial depression.


CONCLUSIONS
These data suggest that adenosine receptor-mediated actions during sepsis affect vascular beds selectively and indicate a significant role for adenosine in resting perfusion redistribution in sepsis.
Motew
S J
SJ
Department of Surgery, University of Illinois College of Medicine at Chicago, Chicago, Illinois, 60612, USA.
Sam
A D
AD
Mourelatos
M G
MG
Sharma
A C
AC
Alden
K J
KJ
Ferguson
J L
JL
Law
W R
WR
D000241:Adenosine / Q000502:physiology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009928:Organ Specificity; D010538:Peritonitis / Q000378:metabolism / Q000503:physiopathology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine