Impact of sex and pathophysiology on optimal drug choice in hypertensive rats: Quantitative insights for precision medicine
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Date
2021-04
Authors
Ahmed, Sameed
Sullivan, Jennifer C.
Layton, Anita T.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Less than half of all hypertensive patients receiving treatment are successful in normalizing their blood pressure. Despite the complexity and heterogeneity of hypertension, the current antihypertensive guidelines are not tailored to the individual patient. As a step toward individualized treatment, we develop a quantitative systems pharmacology model of blood pressure regulation in the spontaneously hypertensive rat (SHR) and generate sex-specific virtual populations of SHRs to account for the heterogeneity between the sexes and within the pathophysiology of hypertension. We then used the mechanistic model integrated with machine learning tools to study how variability in these mechanisms leads to differential responses in rodents to the four primary classes of antihypertensive drugs. We found that both the sex and the pathophysiological profile of the individual play a major role in the response to hypertensive treatments. These results provide insight into potential areas to apply precision medicine in human primary hypertension.
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Keywords
in silico biology, medicine, precision medicine, physiology