In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension

Clinical trials evaluating the efficacy of chronic electrical stimulation of the carotid baroreflex for the treatment of hypertension (HTN) are ongoing. However, the mechanisms by which this device lowers blood pressure (BP) are unclear, and it is uncertain which patients are most likely to receive...

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Autores principales:	John S. Clemmer, W. Andrew Pruett, Robert L. Hester
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/857433f776b44e92a9d7df63a816521f
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spelling	oai:doaj.org-article:857433f776b44e92a9d7df63a816521f2021-11-25T06:19:42ZIn silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension1932-6203https://doaj.org/article/857433f776b44e92a9d7df63a816521f2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601446/?tool=EBIhttps://doaj.org/toc/1932-6203Clinical trials evaluating the efficacy of chronic electrical stimulation of the carotid baroreflex for the treatment of hypertension (HTN) are ongoing. However, the mechanisms by which this device lowers blood pressure (BP) are unclear, and it is uncertain which patients are most likely to receive clinical benefit. Mathematical modeling provides the ability to analyze complicated interrelated effects across multiple physiological systems. Our current model HumMod is a large physiological simulator that has been used previously to investigate mechanisms responsible for BP lowering during baroreflex activation therapy (BAT). First, we used HumMod to create a virtual population in which model parameters (n = 335) were randomly varied, resulting in unique models (n = 6092) that we define as a virtual population. This population was calibrated using data from hypertensive obese dogs (n = 6) subjected to BAT. The resultant calibrated virtual population (n = 60) was based on tuning model parameters to match the experimental population in 3 key variables: BP, glomerular filtration rate, and plasma renin activity, both before and after BAT. In the calibrated population, responses of these 3 key variables to chronic BAT were statistically similar to experimental findings. Moreover, blocking suppression of renal sympathetic nerve activity (RSNA) and/or increased secretion of atrial natriuretic peptide (ANP) during BAT markedly blunted the antihypertensive response in the virtual population. These data suggest that in obesity-mediated HTN, RSNA and ANP responses are key factors that contribute to BP lowering during BAT. This modeling approach may be of value in predicting BAT responses in future clinical studies.John S. ClemmerW. Andrew PruettRobert L. HesterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John S. Clemmer W. Andrew Pruett Robert L. Hester In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension
description	Clinical trials evaluating the efficacy of chronic electrical stimulation of the carotid baroreflex for the treatment of hypertension (HTN) are ongoing. However, the mechanisms by which this device lowers blood pressure (BP) are unclear, and it is uncertain which patients are most likely to receive clinical benefit. Mathematical modeling provides the ability to analyze complicated interrelated effects across multiple physiological systems. Our current model HumMod is a large physiological simulator that has been used previously to investigate mechanisms responsible for BP lowering during baroreflex activation therapy (BAT). First, we used HumMod to create a virtual population in which model parameters (n = 335) were randomly varied, resulting in unique models (n = 6092) that we define as a virtual population. This population was calibrated using data from hypertensive obese dogs (n = 6) subjected to BAT. The resultant calibrated virtual population (n = 60) was based on tuning model parameters to match the experimental population in 3 key variables: BP, glomerular filtration rate, and plasma renin activity, both before and after BAT. In the calibrated population, responses of these 3 key variables to chronic BAT were statistically similar to experimental findings. Moreover, blocking suppression of renal sympathetic nerve activity (RSNA) and/or increased secretion of atrial natriuretic peptide (ANP) during BAT markedly blunted the antihypertensive response in the virtual population. These data suggest that in obesity-mediated HTN, RSNA and ANP responses are key factors that contribute to BP lowering during BAT. This modeling approach may be of value in predicting BAT responses in future clinical studies.
format	article
author	John S. Clemmer W. Andrew Pruett Robert L. Hester
author_facet	John S. Clemmer W. Andrew Pruett Robert L. Hester
author_sort	John S. Clemmer
title	In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension
title_short	In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension
title_full	In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension
title_fullStr	In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension
title_full_unstemmed	In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension
title_sort	in silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/857433f776b44e92a9d7df63a816521f
work_keys_str_mv	AT johnsclemmer insilicotrialofbaroreflexactivationtherapyforthetreatmentofobesityinducedhypertension AT wandrewpruett insilicotrialofbaroreflexactivationtherapyforthetreatmentofobesityinducedhypertension AT robertlhester insilicotrialofbaroreflexactivationtherapyforthetreatmentofobesityinducedhypertension
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In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension

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