Guanylyl cyclase A in Both Renal Proximal Tubular and Vascular Endothelial Cells Protects the Kidney against Acute Injury in Rodent Experimental Endotoxemia models

( Max 2000 Items )
URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28483
Title
Guanylyl cyclase A in Both Renal Proximal Tubular and Vascular Endothelial Cells Protects the Kidney against Acute Injury in Rodent Experimental Endotoxemia models
File
Description

Abstract
WHAT WE ALREADY KNOW ABOUT THIS TOPIC:

WHAT 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.
METHODS:

Normal 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.
RESULTS:

Recombinant 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.
CONCLUSIONS:

Both endogenous and exogenous natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A in proximal tubules and endothelial cells.

(医博甲692)

Author
著者 北村  裕亮
著者(ヨミ) キタムラ ヒロアキ
著者(別表記) Kitamura Hiroaki
Publication Title
Anesthesiology
Volume
129
Issue
2
Start Page
296
End Page
310
Publisher
American Society of Anesthesiologists
Lippincott, Williams & Wilkins
Published Date
2018-08-01
ISSN
0003-3022
PMID
29629958
DOI
10.1097/ALN.0000000000002214
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.1097/ALN.0000000000002214
Text Version
ETD
Grant ID
博甲第692号
Grant Date
2018-06-27
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.