rol del sistema nervioso renal en la hipertensión refractaria

$: Rol del sistema nervioso renal en la hipertensión refractaria$
Rol del sistema nervioso renal en la

hipertensión refractaria

Dr Ramiro Sanchez

Jefe de Hipertension Arterial y Unidad Metabolica Fundacion Favaloro

¿Daño de órgano blanco?

– Cardiopatía– Nefropatía– Neuropatía– Vasculopatía

Comorbilidades

– Tabaquismo– Alcoholismo– Obesidad– Ansiedad– Sedentarismo– Diabetes

Adherencia

Monitoreo constante

Sal

Sodio en

orina24 hs

Secundaria

Investigación de acuerdo a las Guías de Hipertensión

Hipertensión Resistente

Sospecha de Hipertensión Resistente

Descartar pseudoresistencia– Adherencia a tratamiento farmacológico y

no farmacológico– Dosis inadecuada

Descartar efecto de guardapolvo blanco(MAPA24hs)

Nervios Aferentes Renales

The kidney is a source of central sympathetic activity, sending signals to the CNS

Nervios Eferentes Renales

Sympathetic signals from the CNS modulate the physiology of the

kidneys

Inervacion Renal y su conexion con el SNC

Adapted from Schlaich MP, et al. Hypertension. 2009;54:1195-1201.

Blood Pressure Neurohormones

GFRIschemia

Kidney FailureWorsening Kidney Failure

Smooth Muscle Migration

VasoconstrictionAtherosclerosis

Efectos Cardiorenales de la Activación Crónica del

Sistema Nervioso Simpático


HypertrophyIschemia

ArrhythmiaHeart Failure

Worsening HF

S Julius, R Sanchez, et al, Hypertension, Vol.4, 782, 1982

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-10 10 20 30 400 -10 10 20 30 400

Ganglionic Blockade

**

**

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Time (min)

Ganglionic blockade

L. b. compressionLower b. compression

Effects of increased renal sympathetic nerve activity (RSNA) on the 3 renal neuroeffectors: the juxtaglomerular granular cells (JGGC) with increased RSR via stimulation of β-1 adrenoceptors

(β-1-AR), the renal tubular epithelial cells (T) with increased ren...

DiBona G F , and Esler M Am J Physiol Regul Integr Comp Physiol 2010;298:R245-R253

©2010 by American Physiological Society

The relationship between renal nerve stimulation (RNS) frequency and maximum response of renin secretion rate (RSR) (increase), urinary sodium excretion (decrease) and renal blood flow

(RBF) (decrease). [From DiBona GF (10a).].



Influence of renal nerves on relationship between urinary flow rate (%H2O excretion) or urinary sodium excretion (%Na excretion) and renal perfusion pressure (RPP).



Effect of TRPV1 stimulation by capsaicin, either given intrarenally (IRA Cap; n=10) or systemically (IV Cap; n=10).

Ditting T et al. Hypertension 2012;59:467-476

Copyright © American Heart Association

Tonic Postganglionic Sympathetic Inhibition Induced by

Afferent Renal Nerves? Tilmann Ditting, et al.Hypertension. 2012;59:467-476

• RSNA is increased, whereas its control is impaired in arterial hypertension

• The study indicates a direct evidence that afferent intrarenal nerves provide a tonically acting sympathoinhibitory system, which seems to be rather mediated by neurokinin release acting via neurokinin 1 receptor pathways rather than by electric afferent effects on central sympathetic outflow.

Figure 5. Plasma renin activity (upper panel) and plasma concentrations of angiotensin II (middle panel) and aldosterone (lower panel) in the supine position and after 30 minutes of

45° head-up tilt (HUT) with placebo (○) and reboxetine (•). n=10, #P<0.08; ...

Mayer A F et al. Hypertension 2006;48:120-126


Figure 2. RBF and renal vascular resistance in the supine position after ingestion of 8 mg reboxetine (•, drawn line) or placebo (○, dotted line). n=16, *P<0.05 (paired t test).

Mayer A F et al. Hypertension 2006;48:120-126


The “gold standard” electrophysiological and neurochemical methods for studying the human sympathetic nervous system are multiunit postganglionic efferent sympathetic

nerve recording and isotope dilution measurement of norepinephrine release to plasma.

Esler M J Appl Physiol 2010;108:227-237


Grassi G Hypertension 2009;54:690-697


Figure 2. Behavior of muscle sympathetic nerve traffic (MSNA), expressed as bursts incidence corrected for heart rate (bs/100 hb) in mild-to-moderate (MEH) and severe (SEH) hypertension (left panel), in white coat (WCHT) and masked (MHT) hypertension (centr...

Grassi G Hypertension 2009;54:690-697


17

J Hypertens 24:789-801;2006

H y p e r l e p t i n e m i a

A r t e r i a l h y p e r t e n s i o n

Vasoconstriction Na+ retention

Renal Na+, K+ -ATPase

NO

Oxidative stressSNS

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Desnervacion Renal

Blood Pressure Neurohormones

Disrupt the renal nerves,break the cycle

Simultaneously reduce bothefferent & afferent effects


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Baseline

1 Month

12 Months

MSNA

(burst/min)

BP

(mm Hg)

56 161/107

41 141/90 (-20/-17)

19 127/81 (-34/-26)

Improvement in cardiac baroreflex sensitivity after renal denervation (7.8 11.7 msec/mm Hg)

Reduced Sympathetic Nerve Activity After

Catheter-Based Renal Denervation*

New Engl J Med Case Study

*59-year-old male on antihypertensive medications.Schlaich MP, et al. New Engl J Med. 2009;361:932-934.

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Baseline 1 Month ∆

Office BP (mm Hg) 161/107 141/90

Renal NE spillover (ng/min)

• Left kidney 72 37 -48%

• Right kidney 79 20 -75%

Total body NE spillover (ng/min) 600 348 -42%

Plasma renin (μg/l/hr) 0.3 0.15 -50%

Renal plasma flow (mL/min) 719 1126 57%

Left ventricular mass (g/m2) 78.8 73.1 -7%

Changes in Underlying Physiology

Consistent With Renal Denervation*

New Engl J Med Case Study

*59-year-old male on antihypertensive medications.Schlaich MP, et al. New Engl J Med. 2009;361:932-934.

Proportion of patients with normal urinary albumin excretion (UAE), microalbuminuria (MAU), and macroalbuminuria at baseline and 3 and 6 months after renal denervation.

Mahfoud F et al. Hypertension 2012;60:419-424


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• No change in renal function

Symplicity HTN-2 Trial –

Chronic Safety (cont)

∆ Renal Function

(baseline-6M)

Symplicity

Renal

Denervation

Group

Control

Group

Difference

(95% CI) P-value

Mean eGFR ± SD

(mL/min/1.73m2)

0.2 ± 11

(n=49)

0.9 ± 12

(n=51)

-0.7

(-5.4, 3.9)0.76

Mean serum creatine ± SD

(μmol/L)

0.2 ± 17.6

(n=49)

-1.1 ±

10.3

(n=51)

1.3

(-4.5, 7.0)0.67

Mean cystatin-C ± SD

(mg/L)

0.1 ± 0.2

(n=37)

0.0 ± 0.1

(n=40)

0.0

(0.0, 0.1)0.31

Symplicity HTN-2 Investigators. Lancet. 2010;376:1903-1909.

Sympathetic Nervous System and Hypertension, Gerald F. DiBona Hypertension. 2013;61:556-560

Luego de la desnervación renal la actividad SNS aferente y eferente renal disminuye. El descenso de la actividad eferente hacia el riñón se traduce en reducción del sistema RAA renal, reducción de la resistencia vascular renal, incremeneto del flujo sanguineo renal y reducción de la reabsorción de sodio, con normalización de la curva de natriuresis por presión. Todas estas condiciones favorecen el descenso de la presión arterial. Los efectos de la reducción de la actividad aferente desde el riñón se traduce en un descenso de la actividad simpática periférica, descenso de las resistencias vasculares periféricas y del volúmen minuto cardíaco y una posterior reducción de la actividad simpatica sobre el riñón.

ConclusionesEl sistema nervioso simpático aferente renal participa en la regulación del tono vasomotor renal y la homeostasis del sodio

El sistema nervioso eferente renal participa en la regulación de la presión arterial, función cardiovascular y regulación del metabolismo hidrocarbonado

El sistema nervioso renal es uno de los factores que contribuyen a la severidad de la hipertensión arterial en la hipertensión resistente

La desnervación renal puede contribuir eficazmente en el tratamiento de la hipertensión resistente

Figure Digital subtraction angiography Showing (August, 2011) renal denervation at a superior position (position 5 of 6) near the

ostium; and (February, 2012) ostial stenosis and blood pressure gradient across the stenosis.

Oliver Vonend , Gerald Antoch , Lars Christian Rump , Dirk Blondin

Secondary rise in blood pressure after renal denervation

The Lancet Volume 380, Issue 9843 2012 778

http://dx.doi.org/10.1016/S0140-6736(12)61145-3

rol del sistema nervioso renal en la hipertensión refractaria

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