• Hiroaki Kitamura, Daisuke Nakano, Yoshiharu Sawanobori, Takehiko Asaga, Hideki Yokoi, Motoko Yanagita, Masashi Mukoyama, Takeshi Tokudome, Kenji Kangawa, Gotaro Shirakami, and Akira Nishiyama.
• From the Department of Anesthesiology (H.K., Y.S., T.A., G.S.) Department of Pharmacology (D.N., A.N.), Kagawa University, Kagawa Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto (J.N., H.Y., M.Y.) Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto (M.M.) Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Osaka (T.T., K.K.), Japan.
• Anesthesiology. 2018 Aug 1; 129 (2): 296-310.

What We Already Know About This TopicWHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Natriuretic peptides are used, based on empirical observations, in intensive care units as antioliguric treatments. We hypothesized that natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A, a receptor for natriuretic peptides, in proximal tubules and endothelial cells.MethodsNormal Sprague-Dawley rats and mice lacking guanylyl cyclase A in either endothelial cells or proximal tubular cells were challenged with lipopolysaccharide and assessed for oliguria and intratubular flow rate by intravital imaging with multiphoton microscopy.ResultsRecombinant atrial natriuretic peptide efficiently improved urine volume without changing blood pressure after lipopolysaccharide challenge in rats (urine volume at 4 h, lipopolysaccharide: 0.6 ± 0.3 ml · kg · h; lipopolysaccharide + fluid resuscitation: 4.6 ± 2.0 ml · kg · h; lipopolysaccharide + fluid resuscitation + atrial natriuretic peptide: 9.0 ± 4.8 ml · kg · h; mean ± SD; n = 5 per group). Lipopolysaccharide decreased glomerular filtration rate and slowed intraproximal tubular flow rate, as measured by in vivo imaging. Fluid resuscitation restored glomerular filtration rate but not tubular flow rate. Adding atrial natriuretic peptide to fluid resuscitation improved both glomerular filtration rate and tubular flow rate. Mice lacking guanylyl cyclase A in either proximal tubules or endothelium demonstrated less improvement of tubular flow rate when treated with atrial natriuretic peptide, compared with control mice. Deletion of endothelial, but not proximal tubular, guanylyl cyclase A augmented the reduction of glomerular filtration rate by lipopolysaccharide.ConclusionsBoth endogenous and exogenous natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A in proximal tubules and endothelial cells.

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