Aldosterone-induced hypertension is associated with renal damage that may be mediated by endothelin-1 (ET-1). We evaluated whether inflammatory cell infiltration and DNA-binding activity of the transcription factors nuclear factor κB (NF-κB) and activator protein-1 (AP-1) were increased in kidneys from aldosterone-infused rats. The role of ET-1 in these processes was evaluated by treating rats with the ETA-receptor blocker, BMS 182874. Rats were infused with aldosterone (0.75µg/h) via a mini-osmotic pump and were given 1% NaCl in the drinking water in the absence and presence of BMS 182874 or of the aldosterone receptor blocker, spironolactone. Renal sections were used to assess inflammatory cell infiltration, which was identified immunocytochemically using monoclonal antibodies against macrophages (ED1+). Electrophoretic mobility shift assays evaluated the DNA-binding activity of NF-κB and AP-1 in renal tissue. Systolic blood pressure (BP) was increased in the aldosterone-infused group compared with controls (123±6 versus 110±10mmHg, P<0.05). BMS 182874 and spironolactone significantly decreased BP (P<0.05). Macrophage infiltration was increased in the kidneys of aldosterone-infused rats compared with controls. Renal binding activity (arbitrary units) of AP-1, in contrast with that of NF-κB, increased in aldosterone-infused rats compared with control rats (AP-1, 4.2±0.3 versus 1.0±0.1, P<0.05; NF-κB, 1.6±0.5 versus 1.2±0.5). BMS 182874 and spironolactone decreased macrophage infiltration (by 70% and 50% respectively) and AP-1 binding activity (1.0±0.3 and 0.8±0.3 respectively). In conclusion, kidneys from aldosterone-infused rats exhibited macrophage infiltration and increased AP-1 DNA-binding activity. These processes were attenuated by BMS 182874. Our findings suggest that renal damage in aldosterone-dependent hypertension is associated with inflammatory processes that are mediated in part via ET-1.
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September 2002
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Conference Article|
September 01 2002
Contribution of endothelin-1 to renal activator protein-1 activation and macrophage infiltration in aldosterone-induced hypertension
Rita C A TOSTES;
Rita C A TOSTES
*Department of Pharmacology, Instituto de Ciencias Biomedicas, Univeridade de Sao Paulo, Av Lineu Prestes 1524, Sao Paulo 05508-900, Brazil
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Rhian M TOUYZ;
Rhian M TOUYZ
†Clinical Research Institute of Montreal, University of Montreal, 110 Pine Avenue West, Montreal, Québec, Canada H2W 1R7
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Gang HE;
Gang HE
†Clinical Research Institute of Montreal, University of Montreal, 110 Pine Avenue West, Montreal, Québec, Canada H2W 1R7
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Xin CHEN;
Xin CHEN
†Clinical Research Institute of Montreal, University of Montreal, 110 Pine Avenue West, Montreal, Québec, Canada H2W 1R7
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Ernesto L. SCHIFFRIN
†Clinical Research Institute of Montreal, University of Montreal, 110 Pine Avenue West, Montreal, Québec, Canada H2W 1R7
Dr E.L. Schiffrin (e-mail [email protected]).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 25S–30S.
Citation
Rita C A TOSTES, Rhian M TOUYZ, Gang HE, Xin CHEN, Ernesto L. SCHIFFRIN; Contribution of endothelin-1 to renal activator protein-1 activation and macrophage infiltration in aldosterone-induced hypertension. Clin Sci (Lond) 1 September 2002; 103 (s2002): 25S–30S. doi: https://doi.org/10.1042/CS103S025S
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