Interleukin‐1 in chronic angiotensin II‐high salt diet induced hypertension

Abstract

IL‐6 and TNF‐α are implicated in hypertension induced by angiotensin II infusion plus high salt diet (AngII‐HS). Since IL‐1β can stimulate production of both cytokines and is implicated in some renal injury models, we investigated the role of IL‐1β in AngII‐HS hypertension. In rats, 14‐day AngII‐HS (AngII at 65 ng/min s.c. + 8% NaCl diet) increased 24‐h average mean arterial pressure (191±3 vs 108±3 mmHg in normal NaCl control rats [NS], P<0.001) and renal cortical immunoreactive IL‐1β content (44±6 vs 21±3 pg/ml, P<0.01). AngII‐HS rats also displayed significantly increased urinary protein (431±33 mg/d) and albumin excretion (2.5±0.3 mg/d) compared to NS rats (22±6 & 0.8±0.3 mg/d, P<0.001). To test whether IL‐1β contributes to renal injury in AngII‐HS hypertension, the effects of 14‐day AngII‐HS (90 ng/min s.c. + 4% NaCl diet) were compared in wild‐type and IL‐1 receptor −/− mice. After a 24‐h baseline urine collection, mice were randomized to AngII‐HS or NS treatment groups. Baseline urine flow and Na+, protein and albumin excretion rates did not significantly differ between the four groups. At day 14, protein excretion was significantly increased by AngII‐HS in wild‐type and IL‐1 receptor −/− mice (3.7±0.9 & 5.2±1.5 mg/d) compared to NS wild‐type and IL‐1 receptor −/− mice (1.3±0.3 & 0.9±0.1 mg/d; P<0.05), however this effect was not significantly different between genotypes. Similarly, urine flow, Na+ and albumin excretion were significantly increased in AngII‐HS mice compared to NS mice (P<0.05), but there were no differences between genotypes. Preliminary data also suggests that the degree of hypertension induced by AngII‐HS is similar in wild‐type and IL‐1 receptor −/− mice. Our results indicate that although IL‐1β production is increased in the renal cortex in AngII‐HS hypertension, IL‐1 receptor signalling does not appear to contribute to the development of proteinuria in this model.