Renal interstitial concentration of adenosine during endotoxin shock.
The present experiments were designed to measure the renal interstitial concentration of adenosine in an attempt to determine whether adenosine participates in the regulation of renal hemodynamics during endotoxin shock. The renal concentration of adenosine in response to lipopolysaccharide (LPS) administration was measured in anesthetized dogs using a microdialysis method. Renal hemodynamic responses to LPS were also determined with and without the adenosine A(1) receptor antagonist, (E)-(R)-1-[3-(2-phenylpyrazolo[1, 5-a]pyridin-3-yl)acryloyl]pyperidin-2-ylacetic acid (FK352). Intravenous administration of LPS (0.5 mg/kg) significantly decreased renal blood flow and mean arterial pressure. These parameters reached the minimum level at 5-10 min after the LPS administration and then returned to their respective preinjection levels. The renal interstitial concentration of adenosine increased from 118+/-18 to 381+/-46 nM. During treatment with FK352, LPS decreased renal blood flow and mean arterial pressure, however, these reductions were significantly attenuated. LPS also increased adenosine concentration, but its rise was reduced along with the attenuation of LPS-induced renal blood flow reduction. These results suggest that adenosine was involved in LPS-induced renal hemodynamic changes and that FK352 has a protective effect against renal dysfunction during endotoxin shock. Since the adenosine concentration was inversely proportional to renal blood flow levels, it can be assumed that adenosine plays an important role as a mediator, but not as an initiator of renal hemodynamic changes during endotoxin shock.
Nishiyama
A
A
Department of Pharmacology, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Miura
K
K
Miyatake
A
A
Fujisawa
Y
Y
Yue
W
W
Fukui
T
T
Kimura
S
S
Abe
Y
Y
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
C114384:FK 352; D008070:Lipopolysaccharides; D011720:Pyrazoles; D011725:Pyridines; D000241:Adenosine