Protection against age-dependent renal injury in the F344xBrown Norway male rat is associated with maintained nitric oxide synthase

Moningka, Natasha C.; Sasser, Jennifer M.; Croker, Byron P.; Carter, Christy S.; Baylis, Chris

doi:10.1016/j.mad.2010.10.004

Cited by 12 publications

(20 citation statements)

References 32 publications

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“…This is unlikely to be a compensatory response since the increased nNOSβ in the 5/6AI KC does not replace the nNOS∝ in location or function [1,57]. We also recently reported that the senescent Fisher 344/ Brown Norway cross, which develop very mild glomerular damage, exhibits increases in nNOSβ before any falls in nNOS∝ [59]. We are currently investigating whether the increased nNOS β may play a causal role in the injury development.…”

Section: Nos Proteinsmentioning

confidence: 99%

Nitric oxide synthase derangements and hypertension in kidney disease

Baylis

2012

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of Review Nitric oxide (NO) deficiency occurs by multiple mechanisms and contributes to the pathogenesis of progression of chronic kidney disease (CKD) and its cardiovascular complications. This article concentrates on recent developments on the regulation of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) in chronic kidney disease and on the importance of the NO synthases in kidney disease progression, particularly in diabetic nephropathy. Recent Findings The increased plasma ADMA seen in renal disease is generally predictive of severity of CKD progression and cardiovascular risk. However, some assumptions about the control of ADMA have been challenged; the primacy of the kidney as a metabolic organ for plasma ADMA regulation coming under scrutiny and the relative importance of the 2 isoforms of the ADMA-metabolizing enzymes dimethylarginine dimethylaminohydrolases (DDAHs) is being reevaluated. Alterations in nitric oxide synthases also contribute to CKD progression with the endothelial isoform playing a major role in diabetic nephropathy. Summary Improving our understanding of ADMA regulation is important since pharmacologic targeting of DDAH is underway. The major role of eNOS-derived NO in diabetic nephropathy should lead to novel therapies. The beneficial actions of dietary nitrate supplementation on blood pressure and kidney disease are of considerable clinical relevance.

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Section: Nos Proteinsmentioning

confidence: 99%

Nitric oxide synthase derangements and hypertension in kidney disease

Baylis

2012

Current Opinion in Nephrology &Amp; Hypertension

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111

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“…Indeed, we have previously shown that aged Fischer 344 X Brown Norway (F344/BN) rats, while relatively protected from glomerulosclerosis, do demonstrate increased glomerular ischemia/atrophy, tubular atrophy and interstial fibrosis with age [Moningka et al 2010]. Furthermore, when these animals were treated late in life (between 24 and 30 months of age) with the ARB, losartan, this tubule-interstitial injury was prevented, relative to animals treated with the ACEI, enalapril or age-matched controls; although enalapril treated animals consistently showed lowered levels of injury relative to controls [Moningka et al, 2010].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, when these animals were treated late in life (between 24 and 30 months of age) with the ARB, losartan, this tubule-interstitial injury was prevented, relative to animals treated with the ACEI, enalapril or age-matched controls; although enalapril treated animals consistently showed lowered levels of injury relative to controls [Moningka et al, 2010]. Therefore, it is possible that losartan, is a more effective modulatior of ANG II mediated cell signaling processes.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of NF-κB-induced inflammatory responses by angiotensin II antagonists in aged rat kidney

Kim

Heo

Choi

et al. 2011

Experimental Gerontology

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In this study, we explored the mechanisms by which the angiotensin converting enzyme inhibitor (ACEI), enalapril, and the Ang II receptor blocker (ARB), losartan suppress oxidative stress and NF-κB activation-induced inflammatory responses in aged rat kidney. The experimentations were carried out utilizing aged (24-month-old) Brown Norway x Fischer 344 (F1) male rats which were randomized into 3 groups and administered enalapril (40 mg/kg), losartan (30 mg/kg) or placebo for 6 months (daily p.o.). The level of reactive species (RS), peroxynitrite (ONOO−), GSH/GSSG and lipid peroxidation were measured. The activity of the pro-inflammatory transcription factor NF-κB, and gene expression of proteins in upstream signaling cascades were measured by electro-mobility shift assay (EMSA) and Western blotting. Enalapril and losartan differentially attenuated redox imbalance and the redox-sensitive transcription factor, NF-κB pathway. Furthermore, stimulation of the NF-κB activation pathway by phosphorylation of p65 was attenuated by both compounds. Moreover, mediation of phosphorylation of p65 by phosphorylation of IκB kinase αβ (IKKαβ) and mitogen- and stress-activated protein kinase-1 (MSK1), were also inhibited by enalapril and losartan. Finally, both compounds also lowered expression of NF-κB-dependent inflammatory genes, such as cyclooxygenase-2 (COX-2),) and inducible NO synthase (iNOS). Only losartan lowered levels of 5-lipoxygenase (5-LOX). These findings indicate that enalapril and losartan differentially suppress inflammatory responses via inhibition of oxidative stress-induced NF-κB activation in aged rat kidney.

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“…All three strains have age-related reductions in ability to secrete renin (2, 3, 15). On the other hand, the F344xBN rat, which maintains a robust salt appetite response with age, has less incidence of renal pathology (19, 43, 44, 45). Regardless, the waning ability of aging F344xBN rats to respond to body fluid challenges was due more to impairments in behavior than in kidney function.…”

Section: Discussionmentioning

confidence: 99%

“…Like the BN strain, the F344xBN rat has less age-related pathology (e.g., fewer tumors) than the F344 and SD strains (2, 32, 45), and also lives longer in absence of disease (13, 32). In addition, the F334xBN strain is less susceptible to hydronephrosis of the kidney (14, 31) and does not develop glomerular sclerosis (19), both of which may have consequences for studies of body fluid homeostasis. This work tests if the F344xBN strain has significant impairments in thirst- and salt appetite-related behaviors with age.…”

Section: Introductionmentioning

confidence: 99%

Age-related declines in thirst and salt appetite responses in male Fischer 344×Brown Norway rats

Thunhorst

Beltz

Johnson

2014

Physiology & Behavior

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The F344xBN strain is the first generational cross between Fischer 344 (F344) and Brown Norway (BN) rats. The F344xBN strain is widely used in aging studies as it is regarded as a model of “healthy” aging (Sprott, 1991). In the present work, male F344xBN rats aged 4 mo (young, n = 6) and 20 mo (old, n = 9) received a series of experimental challenges to body fluid homeostasis to determine their thirst and salt appetite responses. Corresponding urinary responses were measured in some of the studies. Following sodium depletion, old rats ingested less saline solution (0.3 M NaCl) than young rats on a body weight basis, but both ages drank enough saline solution to completely repair the accrued sodium deficits. Following intracellular dehydration, old rats drank less water than young rats, again on a body weight basis, and were less able than young rats to drink amounts of water proportionate to the osmotic challenge. Compared with young rats, old rats drank less of both water and saline solution after combined food and fluid restriction, and also were refractory to the stimulatory effects of low doses of captopril on water drinking and sodium ingestion. Age differences in urinary water and sodium excretion could not account for the age differences in accumulated water and sodium balances. These results extend observations of diminished behavioral responses of aging animals to the F344xBN rat strain and support the idea that impairments in behavior contribute more to the waning ability of aging animals to respond to body fluid challenges than do declines in kidney function. In addition, the results suggest that behavioral defense of sodium homeostasis is less diminished with age in the F344xBN strain compared to other strains so far studied.

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Protection against age-dependent renal injury in the F344xBrown Norway male rat is associated with maintained nitric oxide synthase

Cited by 12 publications

References 32 publications

Nitric oxide synthase derangements and hypertension in kidney disease

Nitric oxide synthase derangements and hypertension in kidney disease

Inhibition of NF-κB-induced inflammatory responses by angiotensin II antagonists in aged rat kidney

Age-related declines in thirst and salt appetite responses in male Fischer 344×Brown Norway rats

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