Expression of nitric oxide synthase isoforms in the mouse kidney: cellular localization and influence by lipopolysaccharide and Toll-like receptor 4

Abstract

We determined the cellular mRNA expression of all intrarenal nitric oxide (NO)-producing NO synthase (NOS) isoforms, endothelial NOS (eNOS) and neuronal NOS (nNOS) and inducible NOS (iNOS) in kidneys from wild type mice (WT) and immune deficient Toll-like receptor 4 (TLR4) mutant mice, during normal physiological conditions and during a shortterm (6-16 hours) endotoxic condition caused by systemically administered lipopolysaccaride (LPS). Investigations were performed by means of in situ hybridization and polymerase chain reaction amplification techniques. In WT, LPS altered the expression rate of all intrarenal NOS isoforms in a differentiated but NOS-isoform coupled expression pattern, with iNOS induction, and up-and down-regulation of the otherwise constitutively expressed NOS isoforms, e.g. eNOS and nNOS and an iNOS isotype. In TLR4 mutants, LPS caused none or a lowered iNOS induction, but altered the expression rate of the constitutive NOS isoforms. It is concluded that the intrarenal spatial relation of individual NOS-isoforms and their alteration in expression provide the basis for versatile NO-mediated renal actions that may include local interactions between NOS isoforms and their individual NO-target sites, and that the NOSisoform dependent events are regulated by TLR4 during endotoxic processes. These regulatory mechanisms are likely to participate in different pathophysiological conditions affecting NO-mediated renal functions.

Effect of ischemic acute renal damage on the expression of COX-2 and oxidative stress-related elements in rat kidney

“…2G), and HO-1 was observed in proximal tubules (Figs. 2F and 3, C and D), similar to what was reported previously (12,28). In addition, kidneys from rats killed 24 h after I/R showed an increased staining for both proteins compared with their controls (for HO-1 sham: 11,306 Ϯ 2,675 m 2 vs. I/R: 15,667 Ϯ 1,438 m 2 , P ϭ not significant).…”

Renal Histopathology During Experimental Septic Acute Kidney Injury and Recovery*

“…www.ccmjournal.org e65 evidence that renal NOS expression is increased in sepsis (19)(20)(21)(22). In our study, we confirm that renal cortical iNOS, eNOS, and nNOS expression are all increased in septic AKI.…”

Asymmetric Dimethylarginine, Endothelial Dysfunction and Renal Disease

“…In the kidney, where the synthesis of arginine occurs mainly in the proximal tubules, cNOS has been found in the glomerules, vessels and tubular segments including the macula densa and inner medullary segments of the collecting duct system [4,5]. The iNOS isoform has been found in the smooth muscle cells of blood vessels, the distal end of the efferent arteriole and the medullary area of the ascending limb of the loop of Henle [6].…”