Renal bioenergetics during early gram-negative mammalian sepsis and angiotensin II infusion.
OBJECTIVE
To measure renal adenosine triphosphate (ATP) (bioenergetics) during hypotensive sepsis with or without angiotensin II (Ang II) infusion.


METHODS
In anaesthetised sheep implanted with a renal artery flow probe and a magnetic resonance coil around one kidney, we induced hypotensive sepsis with intravenous Escherichia coli injection. We measured mean arterial pressure (MAP), heart rate, renal blood flow RBF and renal ATP levels using magnetic resonance spectroscopy. After 2 h of sepsis, we randomly assigned sheep to receive an infusion of Ang II or vehicle intravenously and studied the effect of treatment on the same variables.


RESULTS
After E. coli administration, the experimental animals developed hypotensive sepsis (MAP from 92 ± 9 at baseline to 58 ± 4 mmHg at 4 h). Initially, RBF increased, then, after 4 h, it decreased below control levels (from 175 ± 28 at baseline to 138 ± 27 mL/min). Despite decreased RBF and hypotension, renal ATP was unchanged (total ATP to inorganic phosphate ratio from 0.69 ± 0.02 to 0.70 ± 0.02). Ang II infusion restored MAP but caused significant renal vasoconstriction. However, it induced no changes in renal ATP (total ATP to inorganic phosphate ratio from 0.79 ± 0.03 to 0.80 ± 0.02).


CONCLUSIONS
During early hypotensive experimental gram-negative sepsis, there was no evidence of renal bioenergetic failure despite decreased RBF. In this setting, the addition of a powerful renal vasoconstrictor does not lead to deterioration in renal bioenergetics.
Howard Florey Institute, Florey Neurosciences Institutes, University of Melbourne, Parkville, VIC, Australia. clive.may@florey.edu.au
Clive N
CN
May
Ken
K
Ishikawa
Li
L
Wan
John
J
Williams
R Mark
RM
Wellard
Gaby S
GS
Pell
Graeme D
GD
Jackson
Rinaldo
R
Bellomo
D000255:Adenosine Triphosphate / Q000652:urine; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D004926:Escherichia coli / Q000472:pathogenicity; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism*; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology*; D012756:Sheep; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000255:Adenosine Triphosphate