Effects of the endothelin-1 receptor antagonist tezosentan on renal blood flow and diuresis during prolonged increased intra-abdominal pressure.
BACKGROUND
It has earlier been shown that increased intra-abdominal pressure (IAP) reduces renal blood circulation and urine output both clinically and experimentally. The aim of this study was to investigate the effect of endothelin-1 inhibition by the endothelin-1 receptor antagonist tezosentan on renal blood circulation and diuresis in pigs subjected to prolonged increased intra-abdominal pressure.


METHODS
The IAP in domestic pigs was maintained at 30 mmHg for 3 h. One group of 10 animals was pre-treated with the endothelin-1 receptor antagonist tezosentan, and then received continuous infusion of tezosentan throughout the experiment. Another group of 10 animals served as control. We measured renal cortex blood flow, plasma renin activity, blood concentrations of endothelin-1 and aldosterone, and diuresis.


RESULTS
The administration of tezosentan to pigs with an IAP of 30 mmHg was followed by reduced arterial pressure, reduced renal cortex blood flow, and reduced diuresis. The plasma renin activity increased markedly, but neither renal vascular resistance nor blood concentration of aldosterone did change significantly.


CONCLUSIONS
Tezosentan reduced the arterial blood pressure, which resulted in decreased renal cortex blood flow, and aggravation of the oliguria usually observed under increased IAP. The plasma renin activity increased, but this was not followed by changes in renal vascular resistance, or blood concentration of aldosterone. The results indicate that drugs, which reduce the arterial pressure, may be harmful to the kidneys under increased IAP.
Surgical Research Laboratory, Institute of Surgical Sciences, The Gade Institute, Haukeland University Hospital, University of Bergen, Bergan, Norway. ffgu@haukeland.no
Fjølnir F
FF
Gudmundsson
Asgaut
A
Viste
Ole L
OL
Myking
Ketil
K
Grong
Leif
L
Bostad
Knut
K
Svanes
D000005:Abdomen; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007672:Kidney Cortex / Q000098:blood supply; D008099:Liver / Q000098:blood supply; D008297:Male; D011312:Pressure; D011725:Pyridines / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology*; D014655:Vascular Resistance
D019332:Endothelin-1; D011725:Pyridines; D013777:Tetrazoles; D000450:Aldosterone; C120582:tezosentan; D012083:Renin