Contrast Medium- and Mannitol-Induced Apoptosis in Heart and Kidney of SHR Rats

Zhang, Jun; Duarte, Cristobal G.; Ellis, Sydney

doi:10.1177/019262339902700406

Cited by 44 publications

(33 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This interaction is evident in SHRs exposed to contrast. These SHRs show an acute worsening of cardiac damage (apoptosis and necrosis of cardiomyocytes) contributing to CI-AKI, as demonstrated by glomerular necrosis and sclerosis, tubular cell apoptosis and necrosis, interstitial lymphocytic infiltration, and apoptosis of endothelial cells and smooth muscle cells in small vessels of the heart and kidney [12,15] .…”

Section: Preexisting Cardiac and Renal Damage In The Shr Closely Resementioning

confidence: 99%

See 1 more Smart Citation

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

Zhang

Fallahzadeh

McCullough³

2016

Cardiorenal Med

View full text Add to dashboard Cite

Background:Although there are some animal models for biomarkers of contrast-induced acute kidney injury (CI-AKI), for cardiorenal syndrome (CRS) and for acute renal failure, the interplay between CI-AKI and CRS has yet to be evaluated. Insight into the pathogenesis of CRS is urgently needed from animal models in order to foster the discovery and implementation of novel biomarkers for this disease. Specially designed animal models for type 1 and 3 CRS, particularly CI-AKI, have not yet emerged. Summary: We hypothesize that the aging male spontaneously hypertensive rat (SHR) is likely to be a suitable model. The SHR model is able to mimic risk factors for preclinical CRS that appears in the clinical setting, specifically hypertension, age, preexisting damage and dysfunction of the heart and kidney, endothelial dysfunction, increased level of reactive oxygen species, decreased level and bioavailability of nitric oxide (NO), impairment of the L -arginine-NO pathway, and insulin resistance. In the SHR, CI-AKI results in a different profile of AKI biomarkers than is seen with preexisting chronic kidney injury. Key Messages: The SHR model can be used to evaluate the interaction between CI-AKI and CRS type 1 and 3 and to verify neutrophil gelatinase-associated lipocalin (NGAL) as a reliable CI-AKI biomarker for clinical application. Further research is warranted with a large number of aging male SHRs to prove NGAL as a sensitive, specific, highly predictive, early biomarker for CI-AKI.

show abstract

Section: Preexisting Cardiac and Renal Damage In The Shr Closely Resementioning

confidence: 99%

“…The aging male spontaneously hypertensive rat (SHR) has been used as a model for evaluating contrast-induced cardiac and renal toxicity [11][12][13][14][15][16] . We, therefore, hypothesize that in the aging male SHR, preexisting chronic heart failure and hypertension can mimic preclinical CRS in the clinical setting.…”

Section: Introductionmentioning

confidence: 99%

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

Zhang

Fallahzadeh

McCullough³

2016

Cardiorenal Med

View full text Add to dashboard Cite

show abstract

“…27 In adult SHR, acute osmotic stress induction by the administration of mannitol activates renal and cardiac apoptosis. 28 The precise involvement of osmotic stress in pathological conditions in this model and its potential role in human hypertension require more investigation.…”

Section: Other Extrinsic Factorsmentioning

confidence: 99%

“…In these regard, some studies have proposed that cytoplasmic proteolysis in cardiac cells is not always accompanied by nuclear fragmentation. 4,28 Thus, other tools beyond TUNEL should be applied for the evaluation of cardiomyocyte apoptosis.…”

Section: Pathophysiological Significancementioning

confidence: 99%

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

et al. 2001

View full text Add to dashboard Cite

Abstract-Hypertensive heart disease is a progressive condition in which the compensatory left ventricular hypertrophy that maintains cardiac output leads to myocardial remodeling, characterized by fibrosis, insufficient vascularization, and alterations in cardiomyocytes, including contractile disturbances, changes in gene expression, and decrease in the number of cells. Structural abnormalities in the myocardial wall accelerate the development of diastolic and systolic dysfunction, resulting in heart failure. Many observations point to the apoptotic cell death of cardiomyocytes as a relevant factor in the transition from compensatory hypertrophy to pump failure in experimental and human hypertension. Potential inducers of cardiomyocyte apoptosis in overloaded hearts include extrinsic factors, such as mechanical forces, neurohormonal activation, oxidative stress, hypoxia, and cytokines. Some lines of evidence indicate that angiotensin II and the overstretching of cardiomyocytes are originally involved in the triggering of apoptosis in hypertension, whereas other factors are being investigated. Furthermore, intracellular changes, such as downregulation of survival proteins or activation of death proteins, seem to play an important role. The assumption that the apoptosis of cardiomyocytes worsens hypertensive heart disease prognosis brings forth new approaches to avoid or slow the transition to pump failure. In this respect, experimental data indicate that currently used antihypertensive drugs interfere with cardiomyocyte apoptosis. Moreover, the knowledge of intracellular apoptotic processes in cardiomyocytes provides novel therapeutic strategies to be added to the multimodal approach in the prevention of heart failure.

show abstract

“…Moreover, our previous study showed that male SHR were more susceptible than WKY rats to the cardiotoxicity of radiocontrasts and the contrast mediums-induced toxicity was associated with apoptosis (Zhang et al, 1999). We reasoned that male SHR could be a suitable animal model for accelerating and amplifying SK&F 95654-induced cardiovascular injury and associated biomarker responses.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms and Biomarkers of Cardiovascular Injury Induced by Phosphodiesterase Inhibitor III SK&F 95654 in the Spontaneously Hypertensive Rat

et al. 2006

View full text Add to dashboard Cite

The cardiovascular injury of the type III selective PDE inhibitor SK&F 95654 was investigated in SHR. Twenty-four hours after a single sc injection of 100 or 200 mg/kg of the drug, rats exhibited cardiomyocyte necrosis and apoptosis, interstitial inflammation, hemorrhage and edema, as well as mesenteric arterial hemorrhage and necrosis, periarteritis, EC and VSMC apoptosis, EC activation, and MC activation and degranulation. Elevated serum levels of cTnT and decreased cTnT immunoperoxidase staining on cardiomyocytes were detected in the drug-treated rats. Serum levels of α 2 -macroglobulin and IL-6 were significantly elevated following drug treatment. NMR spectral patterns of urine samples are significantly different between the drug-treated and control rats. These results indicate that measurement of serum cTnT, acute phase proteins, and cytokines as well as metabonomic urine profiles may serve as potential biomarkers for drug-induced cardiovascular injury in rats. Increased expression of CD63 on MC (tissue biomarker of MC), of nitrotyrosine on MC and EC (an indirect indicator of NO in vivo), and of iNOS on MC and EC (source of NO) suggest that NO produced by activated and degranulated MC as well as activated EC play an important role in SK&F 95654-induced mesenteric vascular injury.

show abstract

Contrast Medium- and Mannitol-Induced Apoptosis in Heart and Kidney of SHR Rats

Abstract: The induction of apoptosis by contrast media (CM) and mannitol (M)

Cited by 44 publications

References 28 publications

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

Mechanisms and Biomarkers of Cardiovascular Injury Induced by Phosphodiesterase Inhibitor III SK&F 95654 in the Spontaneously Hypertensive Rat

Contact Info

Product

Resources

About