IL-1R Mediated Activation of Renal Sensory Nerves in DOCA-Salt Hypertension.
Hypertension
; 81(8): 1811-1821, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38841853
ABSTRACT
BACKGROUND:
Clinical trials of renal denervation for the treatment of hypertension have shown a variety of off-target improvements in conditions associated with sympathetic overactivity. This may be due to the ablation of sympathoexcitatory afferent renal nerves, which are overactive under conditions of renal inflammation. Renal IL (interleukin)-1ß is elevated in the deoxycorticosterone acetate-salt model of hypertension, and its activity may be responsible for the elevation in afferent renal nerve activity and arterial pressure.METHODS:
Continuous blood pressure recording of deoxycorticosterone acetate-salt mice with IL-1R (IL-1 receptor) knockout or antagonism was used individually and combined with afferent renal denervation (ARDN) to assess mechanistic overlap. Protein quantification and histological analysis of kidneys were performed to characterize renal inflammation.RESULTS:
ARDN attenuated deoxycorticosterone acetate-salt hypertension (-20±2-Δmmâ Hg mean arterial pressure [MAP] relative to control at study end) to a similar degree as total renal denervation (-21±2-Δmmâ Hg MAP), IL-1R knockout (-16±4-Δmmâ Hg MAP), or IL-1R antagonism (-20±3-Δmmâ Hg MAP). The combination of ARDN with knockout (-18±2-Δmmâ Hg MAP) or antagonism (-19±4-Δmmâ Hg MAP) did not attenuate hypertension any further than ARDN alone. IL-1R antagonism was found to have an acute depressor effect (-15±3-Δmmâ Hg MAP, day 10) in animals with intact renal nerves but not those with ARDN.CONCLUSIONS:
These findings suggest that IL-1R signaling is partially responsible for the elevated afferent renal nerve activity, which stimulates central sympathetic outflow to drive deoxycorticosterone acetate-salt hypertension.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Presión Sanguínea
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Ratones Noqueados
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Modelos Animales de Enfermedad
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Acetato de Desoxicorticosterona
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Hipertensión
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Riñón
Límite:
Animals
Idioma:
En
Revista:
Hypertension
Año:
2024
Tipo del documento:
Article