Lipopolysaccharide impairs endothelial nitric oxide synthesis in rat renal arteries.
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.
Piepot
H A
HA
Departments of Physiology, Anesthesiology, and Internal Medicine (Intensive Care Unit), Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands. piepot@physiol.med.vu.nl
Boer
C
C
Groeneveld
A B
AB
Van Lambalgen
A A
AA
Sipkema
P
P
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat