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

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Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice
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Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

Published on: February 14, 2021

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John S Clemmer1, W Andrew Pruett1, Robert L Hester1,2

  • 1Department of Physiology and Biophysics, Center for Computational Medicine, University of Mississippi Medical Center, Jackson, MS, United States of America.

Plos One
|November 18, 2021
PubMed

Insights

Electrical stimulation of the carotid baroreflex (BAT) lowers blood pressure in hypertension. Mathematical modeling suggests renal sympathetic nerve activity and atrial natriuretic peptide are key to this effect, aiding patient selection.

Area of Science:

  • Physiological modeling
  • Cardiovascular research
  • Hypertension mechanisms

Background:

  • Chronic electrical stimulation of the carotid baroreflex (BAT) is being evaluated for hypertension (HTN) treatment.
  • The precise mechanisms of blood pressure (BP) reduction and patient selection for BAT remain unclear.

Purpose of the Study:

  • To investigate the mechanisms underlying BP reduction during chronic baroreflex activation therapy (BAT) using a physiological model.
  • To identify key physiological factors contributing to the antihypertensive effects of BAT, particularly in obesity-mediated HTN.

Main Methods:

  • Developed a virtual population (n=6092) using the HumMod physiological simulator by varying 335 model parameters.
  • Calibrated a subset of the virtual population (n=60) using data from hypertensive obese dogs (n=6) undergoing BAT, matching BP, glomerular filtration rate, and plasma renin activity.
  • Simulated the effects of blocking renal sympathetic nerve activity (RSNA) and atrial natriuretic peptide (ANP) secretion during BAT in the virtual population.

Main Results:

  • The calibrated virtual population exhibited responses to chronic BAT that were statistically similar to experimental findings.
  • Blocking RSNA suppression and/or ANP secretion during BAT significantly diminished the antihypertensive response in the virtual population.
  • These results indicate that RSNA and ANP play crucial roles in BP lowering during BAT in obesity-mediated HTN.

Conclusions:

  • In obesity-mediated hypertension, the suppression of RSNA and increased secretion of ANP are critical mechanisms for blood pressure reduction achieved through BAT.
  • Physiological modeling offers a valuable approach for predicting patient responses to BAT and guiding future clinical studies.

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