2000
DOI: 10.1038/labinvest.3780182
|View full text |Cite
|
Sign up to set email alerts
|

Interstitial Fibrosis of Unilateral Ureteral Obstruction is Exacerbated in Kidneys of Mice Lacking the Gene for Inducible Nitric Oxide Synthase

Abstract: SUMMARY:Unilateral ureteral obstruction (UUO) is characterized by decreases in renal function and increases in interstitial fibrosis. Previous studies have indicated that pharmacologic manipulations that increase nitric oxide (NO) are beneficial to the obstructed kidneys. NO is produced from arginine by nitric oxide synthase (NOS), an enzyme that exists in both constitutive and inducible (iNOS) forms. To determine the role of the inducible form of NOS in UUO, we used mice with a targeted deletion of iNOS (iNOS… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

8
45
1

Year Published

2002
2002
2017
2017

Publication Types

Select...
7
2

Relationship

0
9

Authors

Journals

citations
Cited by 65 publications
(54 citation statements)
references
References 39 publications
(36 reference statements)
8
45
1
Order By: Relevance
“…Studies on liver and kidney fibrosis in the iNOS knock-out mouse, and our previous work in Peyronie's disease and its animal models, vaginal fibrosis, aging-related arterial media fibrosis, and in corporal fibrosis, suggests that despite iNOS may be initially induced during an early inflammatory process, its main role is as an antifibrotic agent. 12,13,[24][25][26][27][28][29]32,33,37,38,50 This may occur via cGMP produced by the nitric oxide from iNOS, and/or the nitric oxide can directly reduce collagen synthesis, myofibroblast formation in the interstitial connective tissue, and reactive oxygen species. 26,[30][31][32] In contrast to our study with vardenafil in the BCNR rat, the slight stimulation of iNOS induction by sildenafil in the BCNR animals was not significant.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Studies on liver and kidney fibrosis in the iNOS knock-out mouse, and our previous work in Peyronie's disease and its animal models, vaginal fibrosis, aging-related arterial media fibrosis, and in corporal fibrosis, suggests that despite iNOS may be initially induced during an early inflammatory process, its main role is as an antifibrotic agent. 12,13,[24][25][26][27][28][29]32,33,37,38,50 This may occur via cGMP produced by the nitric oxide from iNOS, and/or the nitric oxide can directly reduce collagen synthesis, myofibroblast formation in the interstitial connective tissue, and reactive oxygen species. 26,[30][31][32] In contrast to our study with vardenafil in the BCNR rat, the slight stimulation of iNOS induction by sildenafil in the BCNR animals was not significant.…”
Section: Discussionmentioning
confidence: 99%
“…[14][15][16][17][18][19][20][21][22][23] The expression of iNOS in certain non-immunological tissues is assumed to be a defense mechanism against fibrosis. [24][25][26][27][28][29] The nitric oxide produced by iNOS, besides inhibiting collagen synthesis and the TGFb1 pathway, also quenches reactive oxygen species, and in some cases, the differentiation of fibroblasts to myofibroblasts, the cells that produce collagen in many fibrotic conditions. [30][31][32] In a recent study, we have shown that the PDE5 inhibitor, vardenafil, given for 45 days in the drinking water to rats subjected to bilateral cavernosal nerve resection (BCNR) [33][34][35] prevented the development of CVOD and the underlying SMC loss and fibrosis in the corpora cavernosa.…”
Section: Introductionmentioning
confidence: 99%
“…Oxidative stress is coupled to hypertension in several models and demonstrated in kidneys with ureteral obstruction (28), where it might impair renal NO production. Treatment modalities that increase NO formation (40) or inhibit oxidative stress (54) are beneficial to the progression of cellular and molecular parameters of tubulointerstitial fibrosis caused by obstruction of the ureter, whereas NO deficiency increases renal damage (21).…”
Section: Discussionmentioning
confidence: 99%
“…First, the fact that general inhibition of the activity of all NOS isoforms, and hence nitric oxide production, by prolonged sustained administration of N(G)-nitro-L-arginine methyl ester to rats, leads to considerable fibrotic degeneration in organs such as the heart, liver and kidney, independent of hemodynamic factors that may contribute to this process. [21][22][23][24][25] Second, specific genetic blockade of iNOS in the iNOS knockout mice leads to exacerbation of experimental fibrosis of the kidney and liver, 26,27 and the chronic inhibition of iNOS activity in rats by N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL) intensifies aging-related fibrosis of the arterial wall and of the experimentally induced Peyronie's disease-like fibrotic plaque in the penis. 28,29 Third, administration of iNOS cDNA in the latter model reduces the fibrotic plaque.…”
Section: Antifibrotic Role Of No Following Cavernosal Nerve Resectionmentioning
confidence: 99%