The intrarenal renin-angiotensin system in hypertension: insights from mathematical modelling.
Angiotensin II
Angiotensin II infusion
Blood pressure regulation
Hypertension
Kidney
Renin-angiotensin system
Journal
Journal of mathematical biology
ISSN: 1432-1416
Titre abrégé: J Math Biol
Pays: Germany
ID NLM: 7502105
Informations de publication
Date de publication:
23 03 2023
23 03 2023
Historique:
received:
10
12
2021
accepted:
21
02
2023
revised:
14
01
2023
entrez:
23
3
2023
pubmed:
24
3
2023
medline:
28
3
2023
Statut:
epublish
Résumé
The renin-angiotensin system (RAS) plays a pivotal role in the maintenance of volume homeostasis and blood pressure. In addition to the well-studied systemic RAS, local RAS have been documented in various tissues, including the kidney. Given the role of the intrarenal RAS in the pathogenesis of hypertension, a role established via various pharmacologic and genetic studies, substantial efforts have been made to unravel the processes that govern intrarenal RAS activity. In particular, several mechanisms have been proposed to explain the rise in intrarenal angiotensin II (Ang II) that accompanies Ang II infusion, including increased angiotensin type 1 receptor (AT1R)-mediated uptake of Ang II and enhanced intrarenal Ang II production. However, experimentally isolating their contribution to the intrarenal accumulation of Ang II in Ang II-induced hypertension is challenging, given that they are fundamentally connected. Computational modelling is advantageous because the feedback underlying each mechanism can be removed and the effect on intrarenal Ang II can be studied. In this work, the mechanisms governing the intrarenal accumulation of Ang II during Ang II infusion experiments are delineated and the role of the intrarenal RAS in Ang II-induced hypertension is studied. To accomplish this, a compartmental ODE model of the systemic and intrarenal RAS is developed and Ang II infusion experiments are simulated. Simulations indicate that AT1R-mediated uptake of Ang II is the primary mechanism by which Ang II accumulates in the kidney during Ang II infusion. Enhanced local Ang II production is unnecessary. The results demonstrate the role of the intrarenal RAS in the pathogenesis of Ang II-induced hypertension and consequently, clinical hypertension associated with an overactive RAS.
Identifiants
pubmed: 36952058
doi: 10.1007/s00285-023-01891-y
pii: 10.1007/s00285-023-01891-y
doi:
Substances chimiques
Peptidyl-Dipeptidase A
EC 3.4.15.1
Angiotensin II
11128-99-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
58Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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