Lipopolysaccharide impairs endothelial nitric oxide synthesis in rat renal arteries

Harro A. Piepot, Christa Boer, A. B.Johan Groeneveld, Antonie A. Van Lambalgen, Pieter Sipkema

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background. Impaired endothelium-dependent vasodilation may contribute to hypoperfusion and failure of abdominal organs, including the kidneys during endotoxin or septic shock. In this study, the short-term (2 h) effects of bacterial lipopolysaccharide (LPS) on endothelium-dependent vasodilation in rat renal and superior mesenteric arteries were documented. Methods. Rat renal and mesenteric arteries were dissected and exposed in vitro to LPS for two hours. The effects of LPS on vascular reactivity were determined and compared with time-matched controls. Endothelial nitric oxide (NO) release was determined using an NO microsensor in adjacent vessel segments. Results. LPS impaired maximal acetylcholine (ACh)-induced endothelium-dependent vasodilation in renal arteries (62.5 ± 8.8% vs. 34.4 ± 7.5% in controls and LPS-exposed arteries), but not in mesenteric arteries. LPS did not alter the sensitivity of renal arteries to exogenous NO. ACh-dependent vasodilation was abolished after blocking NO synthesis with 10-4 mol/L L-NA in control and LPS-incubated renal arteries. When compared with controls, NO release induced by ACh and the receptor-independent calcium ionophore A23187 was significantly decreased (P < 0.05) in LPS-exposed renal segments and was fully abolished in endothelium-denuded segments, indicating that LPS attenuated receptor-dependent as well as receptor-independent endothelial NO release. In contrast, ACh- and A23187-induced NO release was normal in LPS- exposed mesenteric arteries. Conclusions. These results indicate that LPS- induced selective impairment of ACh-induced endothelium-dependent relaxation in rat renal arteries is caused by decreased endothelial NO release. This may contribute to the propensity for acute renal failure during septic shock.

Original languageEnglish
Pages (from-to)2502-2510
Number of pages9
JournalKidney International
Volume57
Issue number6
DOIs
Publication statusPublished - 1 Jan 2000

Cite this

Piepot, Harro A. ; Boer, Christa ; Groeneveld, A. B.Johan ; Van Lambalgen, Antonie A. ; Sipkema, Pieter. / Lipopolysaccharide impairs endothelial nitric oxide synthesis in rat renal arteries. In: Kidney International. 2000 ; Vol. 57, No. 6. pp. 2502-2510.
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abstract = "Background. Impaired endothelium-dependent vasodilation may contribute to hypoperfusion and failure of abdominal organs, including the kidneys during endotoxin or septic shock. In this study, the short-term (2 h) effects of bacterial lipopolysaccharide (LPS) on endothelium-dependent vasodilation in rat renal and superior mesenteric arteries were documented. Methods. Rat renal and mesenteric arteries were dissected and exposed in vitro to LPS for two hours. The effects of LPS on vascular reactivity were determined and compared with time-matched controls. Endothelial nitric oxide (NO) release was determined using an NO microsensor in adjacent vessel segments. Results. LPS impaired maximal acetylcholine (ACh)-induced endothelium-dependent vasodilation in renal arteries (62.5 ± 8.8{\%} vs. 34.4 ± 7.5{\%} in controls and LPS-exposed arteries), but not in mesenteric arteries. LPS did not alter the sensitivity of renal arteries to exogenous NO. ACh-dependent vasodilation was abolished after blocking NO synthesis with 10-4 mol/L L-NA in control and LPS-incubated renal arteries. When compared with controls, NO release induced by ACh and the receptor-independent calcium ionophore A23187 was significantly decreased (P < 0.05) in LPS-exposed renal segments and was fully abolished in endothelium-denuded segments, indicating that LPS attenuated receptor-dependent as well as receptor-independent endothelial NO release. In contrast, ACh- and A23187-induced NO release was normal in LPS- exposed mesenteric arteries. Conclusions. These results indicate that LPS- induced selective impairment of ACh-induced endothelium-dependent relaxation in rat renal arteries is caused by decreased endothelial NO release. This may contribute to the propensity for acute renal failure during septic shock.",
keywords = "Endothelium, Hypoperfusion, Inflammation, Renal failure, Septic shock, Vascular smooth muscle",
author = "Piepot, {Harro A.} and Christa Boer and Groeneveld, {A. B.Johan} and {Van Lambalgen}, {Antonie A.} and Pieter Sipkema",
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Lipopolysaccharide impairs endothelial nitric oxide synthesis in rat renal arteries. / Piepot, Harro A.; Boer, Christa; Groeneveld, A. B.Johan; Van Lambalgen, Antonie A.; Sipkema, Pieter.

In: Kidney International, Vol. 57, No. 6, 01.01.2000, p. 2502-2510.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Lipopolysaccharide impairs endothelial nitric oxide synthesis in rat renal arteries

AU - Piepot, Harro A.

AU - Boer, Christa

AU - Groeneveld, A. B.Johan

AU - Van Lambalgen, Antonie A.

AU - Sipkema, Pieter

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Background. Impaired endothelium-dependent vasodilation may contribute to hypoperfusion and failure of abdominal organs, including the kidneys during endotoxin or septic shock. In this study, the short-term (2 h) effects of bacterial lipopolysaccharide (LPS) on endothelium-dependent vasodilation in rat renal and superior mesenteric arteries were documented. Methods. Rat renal and mesenteric arteries were dissected and exposed in vitro to LPS for two hours. The effects of LPS on vascular reactivity were determined and compared with time-matched controls. Endothelial nitric oxide (NO) release was determined using an NO microsensor in adjacent vessel segments. Results. LPS impaired maximal acetylcholine (ACh)-induced endothelium-dependent vasodilation in renal arteries (62.5 ± 8.8% vs. 34.4 ± 7.5% in controls and LPS-exposed arteries), but not in mesenteric arteries. LPS did not alter the sensitivity of renal arteries to exogenous NO. ACh-dependent vasodilation was abolished after blocking NO synthesis with 10-4 mol/L L-NA in control and LPS-incubated renal arteries. When compared with controls, NO release induced by ACh and the receptor-independent calcium ionophore A23187 was significantly decreased (P < 0.05) in LPS-exposed renal segments and was fully abolished in endothelium-denuded segments, indicating that LPS attenuated receptor-dependent as well as receptor-independent endothelial NO release. In contrast, ACh- and A23187-induced NO release was normal in LPS- exposed mesenteric arteries. Conclusions. These results indicate that LPS- induced selective impairment of ACh-induced endothelium-dependent relaxation in rat renal arteries is caused by decreased endothelial NO release. This may contribute to the propensity for acute renal failure during septic shock.

AB - Background. Impaired endothelium-dependent vasodilation may contribute to hypoperfusion and failure of abdominal organs, including the kidneys during endotoxin or septic shock. In this study, the short-term (2 h) effects of bacterial lipopolysaccharide (LPS) on endothelium-dependent vasodilation in rat renal and superior mesenteric arteries were documented. Methods. Rat renal and mesenteric arteries were dissected and exposed in vitro to LPS for two hours. The effects of LPS on vascular reactivity were determined and compared with time-matched controls. Endothelial nitric oxide (NO) release was determined using an NO microsensor in adjacent vessel segments. Results. LPS impaired maximal acetylcholine (ACh)-induced endothelium-dependent vasodilation in renal arteries (62.5 ± 8.8% vs. 34.4 ± 7.5% in controls and LPS-exposed arteries), but not in mesenteric arteries. LPS did not alter the sensitivity of renal arteries to exogenous NO. ACh-dependent vasodilation was abolished after blocking NO synthesis with 10-4 mol/L L-NA in control and LPS-incubated renal arteries. When compared with controls, NO release induced by ACh and the receptor-independent calcium ionophore A23187 was significantly decreased (P < 0.05) in LPS-exposed renal segments and was fully abolished in endothelium-denuded segments, indicating that LPS attenuated receptor-dependent as well as receptor-independent endothelial NO release. In contrast, ACh- and A23187-induced NO release was normal in LPS- exposed mesenteric arteries. Conclusions. These results indicate that LPS- induced selective impairment of ACh-induced endothelium-dependent relaxation in rat renal arteries is caused by decreased endothelial NO release. This may contribute to the propensity for acute renal failure during septic shock.

KW - Endothelium

KW - Hypoperfusion

KW - Inflammation

KW - Renal failure

KW - Septic shock

KW - Vascular smooth muscle

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U2 - 10.1046/j.1523-1755.2000.00109.x

DO - 10.1046/j.1523-1755.2000.00109.x

M3 - Article

VL - 57

SP - 2502

EP - 2510

JO - Kidney International

JF - Kidney International

SN - 0085-2538

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ER -