Abstract 336: Rats with Adenine-Induced Chronic Renal Failure Develop Low-Renin Hypertension That is Aggravated by High NaCl Diet and Associated with Increased Aortic Stiffness
We have shown that rats with adenine-induced chronic renal failure (A-CRF) develop modest hypertension, left ventricular hypertrophy, and a marked decrease in aortic relaxation rate. The aim of this study was to investigate mechanisms causing hypertension in this model and to assess aortic stiffness by measuring aortic pulse wave velocity (PWV). Male Sprague-Dawley rats were equipped with radiotelemetry probes and subsequently received either chow containing adenine (0.5% for 3 weeks, 0.3% for 2 w., and 0.15% thereafter) or were pair-fed with a normal control diet. At 7 to 11 weeks blood pressure responses to high NaCl diet (4%) and pharmacological interventions were performed. In separate groups aortic PWV was analyzed in isoflurane-anesthetized animals. Values are means±SD. Baseline 24-h mean arterial pressure (MAP) was 101±10 and 119±9 mmHg in controls and A-CRF animals, respectively (P < 0.01). After 5 days of 4% NaCl diet MAP had increased by 24±6 mmHg in A-CRF animals vs. 2±1 mmHg in controls (P<0.001 between groups). Administration of L-NAME in the drinking water (50 mg/kg/day) increased MAP by 37±9 and 24±4 mmHg in A-CRF animals and controls, respectively (P< 0.01 between groups). Candesartan (10 mg/kg by gavage) produced a more pronounced reduction of MAP in controls vs. A-CRF animals (-12±3 vs. -5±5 mmHg, P<0.05). Aortic PWV was elevated in A-CRF rats (5.10±0.51 vs. 4.58±0.17 m/s, P<0.05) although histological analysis did not show aortic calcifications. At sacrifice, plasma levels of creatinine (259±46 vs. 31±2 μM, P<0.001) and asymmetric dimethylarginine (ADMA, 0.65±0.04 vs. 0.45±0.02 μM, P < 0.001) were elevated in A-CRF animals whereas plasma renin activity was markedly suppressed (0.7±0.5 vs. 15.1±7.5 μg/L/h, P<0.001). Hypertension in A-CRF animals is characterized by low renin levels and is aggravated by high NaCl diet suggesting a pathogenic role for hypervolemia secondary to severe renal insufficiency. Although ADMA concentrations were elevated, A-CRF animals showed a more pronounced increase in MAP in response to L-NAME than controls, suggesting that reduced nitric oxide synthase activity was not a major cause of hypertension in this model. Finally, aortic stiffness was elevated in A-CRF animals as indicated by increased aortic PWV.
- © 2012 by American Heart Association, Inc.