Animal Models of Kidney Disease

Mohammed‐Ali, Zahraa; Carlisle, Rachel E.; Nademi, Samera; Dickhout, Jeffrey G.

doi:10.1016/b978-0-12-809468-6.00016-4

Cited by 22 publications

(16 citation statements)

References 397 publications

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“…Previous studies have demonstrated that there are sex differences in the development of hypertension and renal injury in SS rats on either a high salt or high fat diet ( Hinojosa-Laborde et al, 2000 ; Bayorh et al, 2001 ; Gerhold et al, 2007 ; Podesser et al, 2007 ; Turbeville et al, 2020 ; Zhang et al, 2020 ). In contrast to those previous studies, we did not feed our rats a typical high salt diet (4–8% NaCl diet) ( Mohammed-Ali et al, 2017 ), but we will admit that the degree of proteinuria may be elevated in male vs. female SS rats on a lower salt diet containing 1% NaCl. However, other studies have shown no differences in the development of hypertension and renal injury between females and males in the SS strain on high salt diet ( Hinojosa-Laborde et al, 2000 ; Murphy et al, 2012 ).…”

Section: Discussionmentioning

confidence: 94%

Treatment With Gemfibrozil Prevents the Progression of Chronic Kidney Disease in Obese Dahl Salt-Sensitive Rats

et al. 2020

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Recently, we reported that Dahl salt-sensitive leptin receptor mutant (SS LepR mutant) rats exhibit dyslipidemia and renal lipid accumulation independent of hyperglycemia that progresses to chronic kidney disease (CKD). Therefore, in the current study, we examined the effects of gemfibrozil, a lipid-lowering drug (200 mg/kg/day, orally), on the progression of renal injury in SS and SS LepR mutant rats for 4 weeks starting at 12 weeks of age. Plasma triglyceride levels were markedly elevated in the SS LepR mutant strain compared to SS rats (1193 ± 243 and 98 ± 16 mg/day, respectively). Gemfibrozil treatment only reduced plasma triglycerides in the SS LepR mutant strain (410 ± 79 mg/dL). MAP was significantly higher in the SS LepR mutant strain vs. SS rats at the end of the study (198 ± 7 vs. 165 ± 7 mmHg, respectively). Administration of gemfibrozil only lowered MAP in SS LepR mutant rats (163 ± 8 mmHg). During the course of the study, proteinuria increased to 125 ± 22 mg/day in SS rats. However, proteinuria did not change in the SS LepR mutant strain and remained near baseline (693 ± 58 mg/day). Interestingly, treatment with gemfibrozil increased the progression of proteinuria by 77% in the SS LepR mutant strain without affecting proteinuria in SS rats. The renal injury in the SS LepR mutant strain progressed to CKD. Moreover, the kidneys from SS LepR mutant rats displayed significant glomerular injury with mesangial expansion and increased renal lipid accumulation and fibrosis compared to SS rats. Treatment with gemfibrozil significantly reduced glomerular injury and lipid accumulation and improved renal function. These data indicate that reducing plasma triglyceride levels with gemfibrozil inhibits hypertension and CKD associated with obesity in SS LepR mutant rats.

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Section: Discussionmentioning

confidence: 94%

Treatment With Gemfibrozil Prevents the Progression of Chronic Kidney Disease in Obese Dahl Salt-Sensitive Rats

et al. 2020

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“…The SHR strain is considered the best model to mimic primary human hypertension considering a lot of shared features, such as similar dynamics of the disease and the activity of crucial systems, such as the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system (RAAS). Therefore, it is the most commonly used strain to study new antihypertensive drugs ( Sellers et al, 2005 ; Lin et al, 2016 ; Mohammed-Ali et al, 2017 ). However, if our hypothesis is correct, i .…”

Section: Discussionmentioning

confidence: 99%

“…It is generally accepted that essential hypertension is a complex, polygenic disease ( Neutel and Smith, 1999 ). Thus, in our own recent study ( Gawrys et al, 2020a ), we decided to evaluate the effectiveness of EET-A in spontaneously hypertensive rats (SHR), which better mimic human primary hypertension ( Doris, 2017 ; Mohammed-Ali et al, 2017 ). Surprisingly, we found that EET-A given alone to adult hypertensive SHR (10 mg/kg/day) did not exhibit any antihypertensive properties.…”

Section: Introductionmentioning

confidence: 99%

Epoxyeicosatrienoic Acid Analog and 20-HETE Antagonist Combination Prevent Hypertension Development in Spontaneously Hypertensive Rats

et al. 2022

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Numerous studies indicate a significant role for cytochrome P-450-dependent arachidonic acid metabolites in blood pressure regulation, vascular tone, and control of renal function. Epoxyeicosatrienoic acids (EETs) exhibit a spectrum of beneficial effects, such as vasodilatory activity and anti-inflammatory, anti-fibrotic, and anti-apoptotic properties. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that inhibits sodium reabsorption in the kidney. In the present study, the efficiency of EET-A (a stable analog of 14,15-EET) alone and combined with AAA, a novel receptor antagonist of 20-HETE, was tested in spontaneously hypertensive rats (SHR). Adult SHR (16 weeks old) were treated with two doses of EET-A (10 or 40 mg/kg/day). In the following experiments, we also tested selected substances in the prevention of hypertension development in young SHR (6 weeks old). Young rats were treated with EET-A or the combination of EET-A and AAA (both at 10 mg/kg/day). The substances were administered in drinking water for 4 weeks. Blood pressure was measured by telemetry. Once-a-week observation in metabolic cages was performed; urine, blood, and tissue samples were collected for further analysis. The combined treatment with AAA + EET-A exhibited antihypertensive efficiency in young SHR, which remained normotensive until the end of the observation in comparison to a control group (systolic blood pressure, 134 ± 2 versus 156 ± 5 mmHg, respectively; p < 0.05). Moreover the combined treatment also increased the nitric oxide metabolite excretion. Considering the beneficial impact of the combined treatment with EET-A and AAA in young rats and our previous positive results in adult SHR, we suggest that it is a promising therapeutic strategy not only for the treatment but also for the prevention of hypertension.

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“…A well-known spontaneous hypertensive rodent model mainly used in the study of RAAS-induced hypertension is the spontaneous hypertensive rat (SHR) [48]. SHR is originally derived from inbreeding the Wistar–Kyoto (WKY) rats with hypertension, and is suitable for studying either hypertension or renal disease and left ventricular diastolic dysfunction [49,50]. Despite spontaneous hypertension, another primary cause of primary hypertension is obesity, which accounts for 60–75% of primary hypertension cases [51].…”

Section: Physiological Regulation Mechanism In Blood-pressurementioning

confidence: 99%

Exploring a New Natural Treating Agent for Primary Hypertension: Recent Findings and Forthcoming Perspectives

Lin

et al. 2019

JCM

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Primary hypertension describes abnormally-high systolic/diastolic blood pressure in a resting condition caused by various genetic or environmental risk factors. Remarkably, severe complications, such as ischemic cardiovascular disease, stroke, and chronic renal disease have led to primary hypertension becoming a huge burden for almost one-third of the total population. Medication is the major regimen for treating primary hypertension; however, recent medications may have adverse effects that attenuate energy levels. Hence, the search for new hypotensive agents from folk or traditional medicine may be fruitful in the discovery and development of new drugs. This review assembles recent findings for natural antihypertensive agents, extracts, or decoctions published in PubMed, and provides insights into the search for new hypotensive compounds based on blood-pressure regulating mechanisms, including the renin-angiotensin-aldosterone system and the sympathetic/adrenergic receptor/calcium channel system.

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Animal Models of Kidney Disease

Cited by 22 publications

References 397 publications

Treatment With Gemfibrozil Prevents the Progression of Chronic Kidney Disease in Obese Dahl Salt-Sensitive Rats

Treatment With Gemfibrozil Prevents the Progression of Chronic Kidney Disease in Obese Dahl Salt-Sensitive Rats

Epoxyeicosatrienoic Acid Analog and 20-HETE Antagonist Combination Prevent Hypertension Development in Spontaneously Hypertensive Rats

Exploring a New Natural Treating Agent for Primary Hypertension: Recent Findings and Forthcoming Perspectives

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