The SHR as a Small Animal Model for Radiocontrast Renal Failure. Relation of Nephrotoxicity to Animal's Age, Gender, Strain, and Dose of Radiocontrast

Abstract

The male spontaneously hypertensive rat (SHR) Duarte, Zhang, and Ellis induced renal damage (RC-RD) increased as the animals aged. In addition, when the administered dose of RC was repeated a f e r a short interval of only 6 h, the degree of RC-RD increased greatly. In parallel control studies of the infruence of gender and strain on the response to &C in 12-month-old rats, neither hypertensive female SHR nor male normotensive Wstar-Kyoto (WKY) rats demonstrated signiJicant spontaneous renal pathology or the marked susceptibility to RC nephrotoxicity shown by their male SHR counterparts. This small animal model for RC-RD, the mature male SHR, has the distinct advantage that risk factors f o r RC-RD, similar to those characterized in humans for RC-RE develop spontaneously without requiring any special treatment or surgical intervention.

Prediction of Chronic Renal Insufficiency After Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate

“…16 An animal model using old spontaneously hypertensive male rats showed that high osmolar contrast media could enhance the progression of glomerulosclerosis and renal failure. 17 However, the long-term renal prognosis of patients after exposure to contrast media has not been reported well. In the Change in NAG at 24 h after angiography (%) 0.192 0.337…”

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

“…The mean serum Cr concentration increased 0.025 mg/dl/day in older patients for 5 days after contrast exposure, while serum Cr did not increase in younger patients [32] . In the aging male SHR model for CI-AKI, old male rats (10, 12, or 14 months old) were more susceptible to developing CI-AKI than younger males (5 and 8 months old) [12] . In 14-month-old SHRs, urinary albumin excretion was markedly increased as a result of dysfunction of the glomerular capillary filter, increased glomerular albumin permeability, and presumably an increased number of more unselective pores in the glomerular barrier [33] .…”

“…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] .…”

“…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.…”

Radiographic contrast media

“…The long-term renal effects of contrast media are uncertain; HO contrast media may enhance the progression of glomerulosclerosis and renal failure in old and spontaneously hypertensive male rats [38], but the longterm effects of contrast media on renal function in man are unknown.…”