Aminoguanidine attenuates endotoxin-induced mesenteric vascular hyporeactivity.
BACKGROUND
The aim of this study was to investigate the effects of inducible nitric oxide synthase inhibition by aminoguanidine on endotoxin-induced reduction in mesenteric blood flow.


METHODS
Twenty Sprague-Dawley rats (180-230 g) allocated into four groups were administered either Escherichia coli endotoxin 1 mg/kg intraperitoneally or its solvent saline and were pretreated with either aminoguanidine (15 mg/kg intraperitoneally 20 min before and 2 h after endotoxin injection) or saline. Some 4 h after endotoxin injection, animals were anaesthetized, arterial blood pressure and mesenteric blood flow were measured and the resistance in the mesenteric vascular beds was then calculated. The effect of phenylephrine (1-30 microg/kg intravenously) on these parameters was also investigated.


RESULTS
Endotoxin did not significantly modify the mean arterial blood pressure but decreased mesenteric blood flow by increasing the vascular resistance (mean(s.e.m.) 7.8(1.0) versus 13.7(1.2) mmHg per min per ml for control versus endotoxin groups; n = 5, P = 0.0099). Aminoguanidine alone had no effect on either the mean arterial blood pressure or mesenteric blood flow, but it completely blocked the effects of endotoxin. On the other hand, endotoxin significantly attenuated the responsiveness to phenylephrine which was restored by aminoguanidine.


CONCLUSIONS
The present results indicate that endotoxin decreases the mesenteric vascular blood flow by increasing vascular resistance and decreases responsiveness to phenylephrine. The effects of endotoxin were inhibited by aminoguanidine. The mesenteric vasoconstriction in response to endotoxin might not be explained by the overproduction of nitric oxide; other actions of aminoguanidine may explain its inhibitory effect. Presented in part to the 10th Annual Meeting of the Surgical Infection Society - Europe, Istanbul, Turkey, May 1997
Kavuklu
B
B
Departments of General Surgery and Pharmacology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey.
Iskit
A B
AB
Guc
M O
MO
Ilhan
M
M
Sayek
I
I
D000704:Analysis of Variance; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010656:Phenylephrine / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004731:Endotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; C004479:pimagedine