Rats with adenine-induced chronic renal failure develop low-renin, salt-sensitive hypertension and increased aortic stiffness

Abstract

Guron G. Rats with adenine-induced chronic renal failure develop low-renin, salt-sensitive hypertension and increased aortic stiffness. Am J Physiol Regul Integr Comp Physiol 304: R744 -R752, 2013. First published March 20, 2013 doi:10.1152/ajpregu.00562.2012.-Rats with adenine-induced chronic renal failure (A-CRF) develop metabolic and cardiovascular abnormalities resembling those in patients with chronic kidney disease. The aim of this study was to investigate the mechanisms of hypertension in this model and to assess aortic stiffness in vivo. Male Sprague-Dawley rats were equipped with radiotelemetry probes for arterial pressure recordings and received either chow containing adenine or normal control diet. At 7 to 11 wk after study start, blood pressure responses to high NaCl (4%) diet and different pharmacological interventions were analyzed. Aortic pulse wave velocity was measured under isoflurane anesthesia. Baseline 24-h mean arterial pressure (MAP) was 101 Ϯ 10 and 119 Ϯ 9 mmHg in controls and A-CRF animals, respectively (P Ͻ 0.01). After 5 days of a high-NaCl diet, MAP had increased by 24 Ϯ 6 mmHg in A-CRF animals vs. 2 Ϯ 1 mmHg in controls (P Ͻ 0.001). Candesartan (10 mg/kg by gavage) produced a more pronounced reduction of MAP in controls vs. A-CRF animals (Ϫ12 Ϯ 3 vs. Ϫ5 Ϯ 5 mmHg, P Ͻ 0.05). Aortic pulse wave velocity was elevated in A-CRF rats (5.10 Ϯ 0.51 vs. 4.58 Ϯ 0.17 m/s, P Ͻ 0.05). Plasma levels of creatinine were markedly elevated in A-CRF animals (259 Ϯ 46 vs. 31 Ϯ 2 M, P Ͻ 0.001), whereas plasma renin activity was suppressed (0.6 Ϯ 0.5 vs. 12.3 Ϯ 7.3 g·l Ϫ1 ·h Ϫ1 , P Ͻ 0.001). In conclusion, hypertension in A-CRF animals is characterized by low plasma renin activity and is aggravated by high-NaCl diet, suggesting a pathogenic role for sodium retention and hypervolemia probably secondary to renal insufficiency. Additionally, aortic stiffness was elevated in A-CRF animals as indicated by increased aortic pulse wave velocity. chronic kidney disease; adenine; hypertension; pulse wave velocity; aortic stiffness CARDIOVASCULAR (CV) DISEASE is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD) (26). There is a graded and inverse relationship between estimated glomerular filtration rate (GFR) and CV risk that is apparent already when GFR falls below 60 ml·min Ϫ1 ·1.73 m 2 (8), and the majority of CKD patients die from CV events before developing end-stage renal disease (25). Although the pathophysiological mechanisms causing increased CV risk in CKD are complex, elevated aortic pulse wave velocity (PWV), a measure of aortic stiffness, is per se an independent powerful predictor of CV death in patients with end-stage renal disease (1). In CKD patients, aortic PWV has been shown to be correlated to vascular calcification indices (14,23,29), which, in turn, are associated with disorders in bone and mineral metabolism that develop with declining GFR (15). However, increased aortic PWV is associated with mortality also in patient groups with normal kidney function...

High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

“…In addition, there was a strong correlation between the degree of LV general fibrosis and serum levels of cTnT in ACRF rats. In accord with a previous study on this model [12], in which AP was measured continuously by radiotelemetry, ACRF rats developed a marked increase in AP in response to a high-NaCl diet. It is likely that the increase in AP was caused by sodium retention and an expansion of the extracellular fluid volume considering that the GFR values in ACRF rats were only about 15% of those in controls.…”

“…Chronic renal failure was induced by feeding the animals with chow containing adenine as previously described [12,13,14]. At the beginning of the study, the animals were provided with standard pelleted rat chow containing adenine (group ACRF, n = 20) or identical chow without adenine [pair-fed controls (C), n = 19].…”

“…Hence, we have established a rat model of adenine-induced chronic renal failure (ACRF) which bears close resemblance to the uremic syndrome in patients [12,13,14]. In this well-characterized model, rats develop severe renal failure and GFR values are approximately 10% of those in controls [12,13,14]. …”

Renal and Myocardial Histopathology and Morphometry in Rats with Adenine - Induced Chronic Renal Failure: Influence of Gum Acacia

“…GA was effective in ameliorating these actions. The possible mechanisms for this finding have been discussed [15]. Similarly, structural remodeling of the heart characterized by left ventricular hypertrophy (LVH) and expansion of interstitial tissue has been reported in uremic patients [21] and rats with partial renal ablation [22].…”

“…The changes in the renal structure and in the vascular function in rats with adenine - induced CKD have recently been investigated, [8,9,14,15] but as far as we are aware, there are no reports on similar morphometric analysis of the myocardium in this animal model.…”