RESUMEN
The importance of the sympathetic nervous system in essential hypertension has been recognized in 2 eras. The first was in early decades of the 20th century, through to the 1960s. Here, the sympathetic nervous system was identified as a target for the treatment of hypertension, and an extensive range of antiadrenergic therapies were developed. Then, after a period of lapsed interest, in a second era from 1985 on, the development of precise measures of human sympathetic nerve firing and transmitter release allowed demonstration of the importance of neural mechanisms in the initiation and maintenance of the arterial blood pressure elevation in hypertension. This led to the development of a device treatment of hypertension, catheter-based renal denervation, which we will discuss.
Asunto(s)
Hipertensión , Riñón , Simpatectomía , Sistema Nervioso Simpático , Humanos , Presión Sanguínea/fisiología , Hipertensión/fisiopatología , Hipertensión/cirugía , Riñón/inervación , Riñón/fisiopatología , Simpatectomía/métodos , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
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.
Asunto(s)
Presión Sanguínea , Acetato de Desoxicorticosterona , Modelos Animales de Enfermedad , Hipertensión , Riñón , Ratones Noqueados , Animales , Ratones , Riñón/inervación , Riñón/metabolismo , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Hipertensión/metabolismo , Presión Sanguínea/fisiología , Receptores de Interleucina-1/metabolismo , Receptores de Interleucina-1/genética , Masculino , Sistema Nervioso Simpático/fisiopatología , Células Receptoras Sensoriales/metabolismoRESUMEN
Catheter based renal denervation has recently been FDA approved for the treatment of hypertension. Traditionally, the anti-hypertensive effects of renal denervation have been attributed to the ablation of the efferent sympathetic renal nerves. In recent years the role of the afferent sensory renal nerves in the regulation of blood pressure has received increased attention. In addition, afferent renal denervation is associated with reductions in sympathetic nervous system activity. This suggests that reductions in sympathetic drive to organs other than the kidney may contribute to the non-renal beneficial effects observed in clinical trials of catheter based renal denervation. In this review we will provide an overview of the role of the afferent renal nerves in the regulation of renal function and the development of pathophysiologies, both renal and non-renal. We will also describe the central projections of the afferent renal nerves, to give context to the responses seen following their ablation and activation. Finally, we will discuss the emerging role of the kidney as an interoceptive organ. We will describe the potential role of the kidney in the regulation of interoceptive sensitivity and in this context, speculate on the possible pathological consequences of altered renal function.