Lipopolysaccharide impairs endothelial nitric oxide synthesis in rat renalarteries

Background. Impaired endothelium-dependent vasodilation may contribute to h ypoperfusion and failure of abdominal organs, including the kidneys during endotoxin or septic shock. In this study, the short-term (2 h) effects of b acterial 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 vi tro to LPS for two hours. The effects of LPS on vascular reactivity were de termined and compared with time-matched controls. Endothelial nitric oxide (NO) release was determined using an NO microsensor in adjacent vessel segm ents. Results. LPS impaired maximal acetylcholine (ACh)-induced endothelium-depen dent vasodilation in renal arteries (62.5 +/- 8.8% vs. 34.4 +/- 7.5% in con trols and LPS-exposed arteries), but not in mesenteric arteries. LPS did no t alter the sensitivity of renal arteries to exogenous NO. ACh-dependent va sodilation 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 A2 3187 was significantly decreased (P < 0.05) in LPS-exposed renal segments a nd 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 L PS-exposed mesenteric arteries. Conclusions. These results indicate that LPS-induced selective impairment o f ACh-induced endothelium-dependent relaxation in rat renal arteries is cau sed by decreased endothelial NO release. This may contribute to the propens ity for acute renal failure during septic shock.