Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase

Knotek, Mladen; Rogachev, Boris; Wang, Wei; Ecder, Tevfik; Melnikov, Vyacheslav Y.; Gengaro, Patricia E.; Esson, Matthew; Edelstein, Charles L.; Dinarello, Charles A.; Schrier, Robert W.

doi:10.1046/j.1523-1755.2001.00740.x

Cited by 186 publications

(148 citation statements)

References 23 publications

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“…However, apart from increasing MAP, this selective inhibitor of iNOS offered little advantage to the kidneys as compared with saline resuscitation (64). In agreement, the degree of renal failure after LPS infusion was similar in iNOS knockout mice as compared with wild-type mice (43).…”

Section: Inhibition Of Nitric Oxide Synthasesupporting

confidence: 54%

“…Specifically for the kidney, passive immunization to TNF-␣ prevented renal cortical damage during endotoxemia in rhesus monkeys (42). Neutralization of TNF-␣ with a TNF-soluble receptor protected mice against LPS-induced renal failure (43). Mice with a targeted deletion of TNF receptor-1 (TNFR1 Ϫ/Ϫ ) were resistant to LPS-induced renal failure (44).…”

Section: Specific Pharmacologic Treatmentmentioning

confidence: 99%

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Prevention and Treatment of Acute Renal Failure in Sepsis

Vriese

2003

Journal of the American Society of Nephrology

113

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Section: Inhibition Of Nitric Oxide Synthasesupporting

confidence: 54%

Section: Specific Pharmacologic Treatmentmentioning

confidence: 99%

Prevention and Treatment of Acute Renal Failure in Sepsis

Vriese

2003

Journal of the American Society of Nephrology

113

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“…Endotoxemia, a major component of sepsis, is associated with an increase in inducible NO synthase (6,7,8,16). In the mouse model used in the present study, a significant rise in plasma NO has been demonstrated at 16 h, and this increase in NO does not occur in inducible NO synthase knockout mice (7).…”

Section: Discussionmentioning

confidence: 56%

“…A significant decrease in glomerular filtration rate (GFR) and renal blood flow (RBF) occurs in the absence of a fall in blood pressure (7). We hypothesized that endotoxemia may be associated with normal blood pressure because of activation of the sympathetic nervous system and renin-angiotensin system (RAS), which secondarily causes renal vasoconstriction.…”

mentioning

confidence: 99%

Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice

Wang

Falk

Jittikanont

et al. 2002

American Journal of Physiology-Renal Physiology

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Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice. Am J Physiol Renal Physiol 283: F583-F587, 2002. First published March 12, 2002 10.1152/ajprenal.00270.2001.-Acute renal failure (ARF) contributes substantially to the high morbidity and mortality observed during endotoxemia. We hypothesized that selective blockade of the renal nerves would be protective against ARF during the early (16 h) stage of endotoxemia [5 mg lipopolysaccharide (LPS)/kg ip in mice]. At 16 h after LPS, there was no change in mean arterial pressure, but plasma epinephrine (4,604 Ϯ 719 vs. 490 Ϯ 152 pg/ml, P Ͻ 0.001), norepinephrine (2,176 Ϯ 306 vs. 1,224 Ϯ 218 pg/ml, P Ͻ 0.05), and plasma renin activity (40 Ϯ 5 vs. 27 Ϯ 2 ng⅐ ml Ϫ1 ⅐ h Ϫ1 , P Ͻ 0.05) were higher in the LPStreated vs. control mice. The high plasma renin activity level decreased to the control level with renal denervation in endotoxemic mice. After intravenous injection of phentolamine (200 g/kg), the decrement in mean arterial pressure was significantly greater in LPS-treated vs. control mice (19.4 Ϯ 3.5 vs. 8.1 Ϯ 1.5 mmHg, P Ͻ 0.01). Sixteen hours after LPS administration, there were significant decreases in glomerular filtration rate (52 Ϯ 18 vs. 212 Ϯ 23 l/min, P Ͻ 0.01) and renal blood flow (0.58 Ϯ 0.08 vs. 0.85 Ϯ 0.06 ml/min, P Ͻ 0.01) in sham-operated mice. The decrement in glomerular filtration rate during endotoxemia was significantly attenuated in mice with denervated kidneys (32 vs. 79%). Moreover, there was no change in renal blood flow during endotoxemia in mice with renal denervation. The present results therefore demonstrate a protective role of renal denervation during normotensive endotoxemia-related ARF in mice, an effect that may be, at least in part, due to a diminished activation of the renin-angiotensin system. glomerular filtration rate; renal blood flow; epinephrine; norepinephrine; sepsis SEPSIS IS THE MOST FREQUENT CAUSE of acute renal failure (ARF) in intensive care units (1, 2, 9). When sepsis is associated with ARF, the mortality may be as high as 80%. The pathogenetic factors responsible for sepsisrelated ARF, however, are incompletely defined. Although ARF may occur with septic shock, it is also clear that sepsis-related ARF can occur in the absence of hypotension (1, 11).In recent studies from our laboratory, a mouse model of endotoxemia-related ARF has been studied. A significant decrease in glomerular filtration rate (GFR) and renal blood flow (RBF) occurs in the absence of a fall in blood pressure (7). We hypothesized that endotoxemia may be associated with normal blood pressure because of activation of the sympathetic nervous system and renin-angiotensin system (RAS), which secondarily causes renal vasoconstriction. The roles of renal nerves and the RAS in this early renal vasoconstriction during endotoxemia, however, have not been investigated. The present investigation was therefore undertaken in a normotensive mouse model of endotoxemia-induced ARF to examine the effect of selective r...

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“…Cytokines, especially TNF-␣ and IL-1, have been shown to be critical mediators of septic shock and ARF (47,48). However, anti-TNF and anti-IL-1 therapies result in little benefit for patients with severe sepsis.…”

Section: Discussionmentioning

confidence: 99%

Thromboxane Receptor Mediates Renal Vasoconstriction and Contributes to Acute Renal Failure in Endotoxemic Mice

Boffa

Just²,

Coffman

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Sepsis is a major cause of acute renal failure (ARF) and death. Thromboxane A2 (TxA 2 ) may mediate decreases of renal blood flow (RBF) and/or GFR associated with LPSinduced sepsis. This study tested whether TxA 2 receptor blockade, with the use of TxA 2 receptor knockout (TP-KO) mice or a selective TP receptor antagonist (SQ29,548), would alleviate LPS-induced renal vasoconstriction and ARF. Under basal conditions, anesthetized TP-KO mice displayed a lower mean arterial pressure than wild-type (WT) mice (102 versus 94 mmHg; P Ͻ 0.05). RBF, renal vascular resistance (RVR), GFR, and urine flow did not differ among groups under basal conditions, suggesting little tonic influence of TxA 2 on renal TP receptors in health. In endotoxemic WT mice, 14 h after LPS (Escherichia coli LPS 8.5 mg/kg intraperitoneally), mean arterial pressure was reduced to 85 mmHg (P Ͻ 0.001), as were RBF (5.0 versus 9.3 ml/min per g kidney wt; P Ͻ 0.001) and GFR (0.38 versus 1.03 ml/min per g kidney wt; P Ͻ 0.001). Heart rate and RVR (71 versus 47 mmHg/ml per min; P Ͻ 0.05) increased. The decreases in RBF and GFR after LPS were attenuated in TP-KO mice versus WT mice (both P Ͻ 0.05). In both TP-KO and TP antagonist-treated mice, RVR remained stable in response to LPS versus WT mice that did not receive LPS. Delayed TP-antagonist treatment (12 h after LPS injection) ameliorated RBF and RVR but did not restore GFR. In other WT animals, TP-antagonist treatment for 2 h before intravenous LPS abolished the early renal vasoconstriction and alleviated the decrease in GFR. These results demonstrate that renal vasoconstriction during endotoxemic shock induced by LPS is mediated by TP receptors as indicated by pharmacologic blockade and genetic disruption of TP receptors.

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Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase

Cited by 186 publications

References 23 publications

Prevention and Treatment of Acute Renal Failure in Sepsis

Prevention and Treatment of Acute Renal Failure in Sepsis

Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice

Thromboxane Receptor Mediates Renal Vasoconstriction and Contributes to Acute Renal Failure in Endotoxemic Mice

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