Natriuresis induced by angiotensin II infusion is attenuated in knockout mice lacking tumor necrosis factor‐α receptors

Abstract

Angiotensin II (AngII) induces the production of tumor necrosis factor‐α (TNF‐α) which causes reduction in renal blood flow (RBF) as well as natriuresis. To assess the contribution of TNF‐α in the renal actions of AngII, the responses to AngII infusion (1 ng/min/g for 30 min, iv) were evaluated in anesthetized knockout mice lacking TNF‐α receptor type 1 (R1KO, n=6) and type 2 (R2KO, n=6) and compared these responses with those in wild type (WT, n=6) mice. Arterial pressure (AP) was recorded from a cannula placed in the carotid artery. RBF and glomerular filtration rate (GFR) were measured by PAH and inulin clearances respectively. Urine was collected from a catheter placed in the bladder. Basal mean AP was lower in R1KO (81±3 mmHg) but not in R2KO (90±4 mmHg) compared to WT (92±4 mmHg). AngII caused similar increases in AP (WT, 37±5%; R1KO, 38±4%; R2KO, 30±4%) in these mice. The AngII induced reductions in RBF (−39±5%) and GFR (−17±7%) in WT were also not significantly different in R1KO (−28±7% and −17±7%) and R2KO (−31±4% and −12±7%). However, despite similar increases in AP, AngII induced natriuresis was significantly attenuated in RIKO (Δ, 2.5±0.9 μmol/min/g) compared to that in WT (Δ, 6.0±0.9 μmol/min/g) and in R2KO (Δ, 4.1±0.4 μmol/min/g). These data indicate that the natriuresis induced by AngII infusion is, at least partly, mediated by concomitant production of TNF‐α acting mainly via the receptor type 1.