Article

Neural mechanisms in human obesity-related hypertension.

Baker Medical Research Institute and Alfred Baker Medical Unit, Alfred Hospital, Melbourne, Australia.
Journal of Hypertension (Impact Factor: 4.22). 09/1999; 17(8):1125-33. DOI: 10.1097/00004872-199917080-00012
Source: PubMed

ABSTRACT Two hypotheses concerning mechanisms of weight gain and of blood pressure elevation in obesity were tested. The first hypothesis is that in human obesity sympathetic nervous system underactivity is present, as a metabolic basis for the obesity. The second hypothesis, attributable to Landsberg, is that sympathetic nervous activation occurs with chronic overeating, elevating blood pressure. These are not mutually exclusive hypotheses, since obesity is a heterogeneous disorder.
Whole body and regional sympathetic nervous system activity, in the kidneys and heart, was measured at rest using noradrenaline isotope dilution methodology in a total of 86 research voluteers in four different subject groups, in lean and in obese people who either did, or did not, have high blood pressure.
In the lean hypertensive patients, noradrenaline spillover for the whole body, and from the heart and kidneys was substantially higher than in the healthy lean volunteers. In normotensive obesity, the whole body noradrenaline spillover rate was normal, mean renal noradrenaline spillover was elevated (twice normal), and cardiac noradrenaline spillover reduced by approximately 50%. In obesity-related hypertension, there was elevation of renal noradrenaline spillover, comparable to that present in normotensive obese individuals but not accompanied by suppression of cardiac noradrenaline spillover, which was more than double that of normotensive obese individuals (P<0.05), and 25% higher than in healthy volunteers. There was a parallel elevation of heart rate in hypertensive obese individuals.
The sympathetic underactivity hypothesis of obesity causation now looks untenable, as based on measures of noradrenaline spillover, sympathetic nervous system activity was normal for the whole body and increased for the kidneys; the low sympathetic activity in the heart would have only a trifling impact on total energy balance. The increase in renal sympathetic activity in obesity may possibly be a necessary cause for the development of hypertension in obese individuals, although clearly not a sufficient cause, being present in both normotensive and hypertensive obese individuals. The discriminating feature of obesity-related hypertension was an absence of the suppression of the cardiac sympathetic outflow seen in normotensive obese individuals. Sympathetic nervous changes in obesity-related hypertension conformed rather closely to those expected from the Landsberg hypothesis.

0 Bookmarks
 · 
95 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: L a fuerte asociación entre obesidad e hipertensión se ha documentado ampliamente en estudios transver-sales de la población general 1-3 . La prevalencia exac-ta de la hipertensión asociada con la obesidad varía con la definición de hipertensión y de obesidad, pero se ha calcu-lado que el riesgo de hipertensión en obesos es de un 50% a un 300% mayor que en individuos con peso normal 2,3 . Hay varias líneas de evidencia, epidemiológicas y experi-mentales que destacan que hay una relación estrecha entre Original Este estudio fue realizado para evaluar los mecanismos de reducción de la presión arterial (PA) inducidos por la pérdi-da de peso, centrándose en particular en las contribuciones de la actividad del sistema nervioso simpático, de la insuli-na y la leptina plasmáticas en ayunas a los valores de la PA, y delinear la influencia adicional del tratamiento farmaco-lógico antihipertensivo. Cinco grupos de obesos hipertensos fueron tratados con el bloqueante de los canales de calcio (BCC) de acción prolongada amlodipina, con el inhibidor de la enzima conversora de angiotensina (ECA) enalapril con o sin un programa de reducción de peso o con un pro-grama de reducción de peso sólo. La PA objetivo fue menor de 140/90 mm Hg para los grupos de tratamiento farmaco-lógico. Los grupos del programa de reducción de peso con o sin tratamiento farmacológico se dividieron en dos gru-pos: grupos con pérdida de peso que consiguieron reducir-lo (≥ 10%) y grupos sin pérdida de peso que no consiguie-ron reducirlo (< 10%) en los 6 primeros meses. La dosis final de BCC y del inhibidor de la ECA fueron menores en los grupos con tratamiento farmacológico y pérdida de peso que en los grupos con tratamiento far-macológico sólo o en los grupos de tratamiento farmacoló-gico y sin pérdida de peso. En los grupos de reducción de peso, independientemente del tratamiento farmacológico, la reducción en porcentaje desde el origen en la insulina plasmática, leptina y nora-drenalina (NA) fueron mayores en los grupos con pérdida de peso (≥ 10%) que en los grupos sin pérdida de peso (< 10%). Las reducciones de NA, insulina y leptina plasmáti-cas fueron significativamente mayores y más rápidas en los grupos con combinación de tratamiento farmacológico y pérdida de peso que en los grupos con tratamiento far-macológico sólo. En los grupos que recibieron el inhibidor de la ECA, las reducciones de NA e insulina plasmáticas y, especialmente, de leptina fueron mayores que en los otros grupos. El grupo que recibió BCC sólo se produjeron reducciones de insulina y leptina, pero no hubo variaciones en la NA plasmática. Las reducciones de insulina y leptina en los grupos que recibieron BCC fueron menores y se produjeron más tarde que en los grupos que recibieron el inhibidor de la ECA o en el grupo de reducción de peso sólo. Estos resultados demuestran que la pérdida de peso se aso-cia con mejorías metabólicas y que estas mejorías se incre-mentan cuando se combinan con tratamiento farmacológi-co. Por tanto, la pérdida de peso debe considerarse como un componente esencial de cualquier programa de tratamiento de la hipertensión asociada a la obesidad. Un resultado ori-ginal de este estudio es que la inhibición por la ECA tiene un efecto sorprendente para reducir la leptina plasmática. La supresión de la actividad simpática, de la insulinemia y de la leptinemia parece desempeñar un papel importante en la reducción de la PA que acompaña a la pérdida de peso. Am J Hypertens 2001; 14: 530-8.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Resistant hypertension is associated with chronic activation of the sympathetic nervous system resulting in various comorbidities. The prevalence of resistant hypertension is often under estimated due to various reasons. Activation of sympathetic nervous system at the renal- as well as systemic- level contributes to the increased level of catecholamines and resulting increase in the blood pressure. This increased activity was demonstrated by increased muscle sympathetic nerve activity and renal and total body noradrenaline spillover. Apart from the hypertension, it is hypothesized to be associated with insulin resistance, congestive heart failure and obstructive sleep apnea. Renal denervation is a novel procedure where the sympathetic afferent and efferent activity is reduced by various techniques and has been used successfully to treat drug-resistant hypertension improvement of various metabolic derangements. Renal denervation has the unique advantage of offering the denervation at the renal level, thus mitigating the systemic side effects. Renal denervation can be done by various techniques including radiofrequency ablation, ultrasound guided ablation and chemical ablation. Various trials evaluated the role of renal denervation in the management of resistant hypertension and have found promising results. More studies are underway to evaluate the role of renal denervation in patients presenting with resistant hypertension in different scenarios. Appropriate patient selection might be the key in determining the effectiveness of the procedure.
    World journal of cardiology. 08/2014; 6(8):814-23.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Renal denervation reduces blood pressure in animals with experimental hypertension and recently catheter based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. However, the randomised, sham controlled Symplicity HTN-3 trial failed to meet its primary efficacy end point, but there is evidence that renal denervation was incomplete in many patients. Currently there is little information regarding the effectiveness of catheter based renal denervation and of the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and functional and anatomical reinnervation at 5.5 and 11 months post-denervation. In anaesthetised, non-denervated sheep there was a high level of renal sympathetic nerve activity (RSNA), and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, RSNA and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, RSNA was present and the responses to electrical stimulation were normal, indicating reinnervation. Anatomical measures of renal innervation by sympathetic efferent nerves (tissue noradrenaline and tyrosine hydroxylase) and afferent sensory nerves (calcitonin gene related peptide) demonstrated large decreases one week post-denervation, but normal levels at 11 months post-denervation. In summary, catheter based renal denervation is effective, but reinnervation occurs. Studies of central and renal changes post-denervation are required to understand the causes of the prolonged hypotensive response to catheter based renal denervation in human hypertension. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Experimental physiology 01/2015; · 2.87 Impact Factor