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

Abstract

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.

Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension

“…Our data supported the coexistence of cardiac and renal damage in SHR [20,23,30,[36][37][38]. Histologically, we confirmed glomerular and tubular lesions in hypertensive conditions [1,5,23].…”

“…The SHR is a reliable model of a spontaneously developing pressure load similar to human essential hypertension; thus, it is usually recognized that the SHR represents an analog of essential hypertension in humans [21,22]. Severe hypertension arises in 100% of SHR with a systolic blood pressure of 180 mmHg or higher [23].…”

Pathological cardiac remodeling occurs early in CKD mice from unilateral urinary obstruction, and is attenuated by Enalapril

“…Myocardial dysfunction occurs prior to changes in ventricular geometry in mice with chronic kidney disease (CKD). However, many animal and clinical studies have focused on uremic cardiomyopathy in advanced CKD (type 4 and 5) or in patients on dialysis 28 , 29 , 59 .…”

Role and Mechanism of the Renin-Angiotensin-Aldosterone System in the Onset and Development of Cardiorenal Syndrome

“…ED often leads to lower GFR and diuretic effects, which cause fluid retention and an increased preload [ 65 ]. Human and rat studies show that ED can also lead to decreased eNOS expression and thus induce reduced expression of vasodilation factors, such as NO; abnormal endothelium-dependent vasodilation; and the onset of arteriosclerosis and calcification [ 66 , 67 ]. ED in animal is a key process involved in the development of CRS, and it plays a vital role in the connection between cardiovascular disease and CKD ( Figure 2 ) [ 68 ].…”