Adenosine receptor antagonism affects regional resting vascular resistanceduring rat peritoneal sepsis

Background. To identify vascular beds where endogenous adenosine plays a si gnificant role as a mediator of resting perfusion alterations associated wi th sepsis, we tested the hypothesis that adenosine receptor blockade would cause differential regional increases in vascular resistance during intrape ritoneal (ip) sepsis in the rat. Materials and methods. Rats (250-350 g) were catheterized and randomized to septic or nonseptic groups. Sepsis was induced with an ip injection of cec al slurry (150 mg/kg in D5W; 5 ml/kg), and baseline hemodynamics, cardiac o utput (CO), and blood flows (microspheres) were measured 24 h later. Animal s then received the adenosine receptor antagonist 8-phenyltheophylline (8-P TH; 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 sk eletal muscle, hepatic portal, and cerebral vascular resistance with concom itant decreases in CO when compared with vehicle at 1 min. No significant r esistance changes were observed in the renal, adipose, or coronary vasculat ures. Adenosine receptor blockade caused a significant increase in +dP/dt a nd -dP/dt during sepsis, indicating that the reduced CO was not secondary t o myocardial depression. Conclusions. These data suggest that adenosine receptor-mediated actions du ring sepsis affect vascular beds selectively and indicate a significant rol e for adenosine in resting perfusion redistribution in sepsis. (C) 1998 Aca demic Press.