Vascular hyporesponsiveness of the renal circulation during endotoxemia in anesthetized pigs

OBJECTIVE: To compare the vascular reactivity of the renal circulation in control and septic conditions. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized pigs (n = 17). INTERVENTIONS: Ten pigs received a continuous intravenous infusion of endotoxin from Escherichia coli (160 ng x kg(-1) x hr(-1)) during 18 hrs, whereas seven control animals received a saline infusion. To test the vascular reactivity, norepinephrine (NE) (1 microg x kg(-1)), acetylcholine (10 microg x kg(-1)), and sodium nitroprusside (10 microg x kg(-1)) were intravenously injected for 20 secs and changes of mean arterial pressure and renal blood flow were observed during the 200 secs after the drug administration. To compare the evolution of the vascular reactivity over time, three tests were performed 5 hrs, 11 hrs, and 17 hrs after initial endotoxin or saline administration. MEASUREMENTS AND MAIN RESULTS: Endotoxin infusion induced a hypotensive and hypokinetic syndrome with renal hypoperfusion. The mean arterial pressure increase after NE injection and the mean arterial pressure decrease after acetylcholine and nitroprusside were lower in endotoxin than in control pigs. In the renal circulation, the increase of resistance after NE injection and the decrease of renal resistance after acetylcholine and nitroprusside injections were lower in endotoxin than in control pigs. CONCLUSIONS: This study shows a hyporesponsiveness of the renal circulation to vasoactive agents during endotoxemia. Vasoconstriction to NE, endothelium-dependent as well as endothelium-independent relaxations are altered during endotoxemia but not abolished, and despite the continuous infusion of endotoxin for 18 hrs, no recovery was observed over time.