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Am J Physiol Heart Circ Physiol. 2019 Aug 30. doi: 10.1152/ajpheart.00354.2019. [Epub ahead of print]

Preeminent Role of the Cardiorenal Axis in the Antihypertensive Response to an Arteriovenous Fistula: An In Silico Analysis.

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Physiology & Biophysics, Univiersity of Mississippi Medical Center, United States.
Department of Physiology and Biophysics, University of Mississippi Medical Center, United States.
of Physiology and Biophysics, University of Mississippi Medical Center, United States.
Department of Physiology & Biophysics, University of Mississippi Medical Center, United States.


Percutaneous creation of a small central arteriovenous (AV) fistula is currently being evaluated for the treatment of uncontrolled hypertension (HT). Although the mechanisms that contribute to the antihypertensive effects of the fistula are unclear, investigators have speculated that chronic blood pressure (BP) lowering may be due to: 1) reduced total peripheral resistance (TPR), 2) increased secretion of atrial natriuretic peptide (ANP), and/or 3) suppression of renal sympathetic nerve activity (RSNA). We used an established integrative mathematical model of human physiology to investigate these possibilities from baseline conditions that mimic sympathetic overactivity and impaired renal function in patients with resistant HT. After simulating a small fistula there were sustained increases in cardiac output, atrial pressures, and plasma ANP concentration (3-fold), without suppression of RSNA; at 8 weeks BP was reduced 14 mmHg along with a 32% fall in TPR. In contrast, when this simulation was repeated while clamping ANP at baseline BP decreased only 4 mmHg, despite a comparable fall in TPR. Further, when chronic resetting of atrial mechanoreceptors was prevented during the fistula RSNA decreased 7% and, along with the same 3-fold increase in ANP, BP fell 19 mmHg. This exaggerated fall in BP occurred with a similar decrease in TPR when compared to the above simulations. These findings suggest that ANP, but not TPR, is a key determinant of long-term BP lowering after the creation of an AV fistula and support a contribution of suppressed RSNA if resetting of the atrial-renal reflex is truly incomplete.


arteriovenous fistula; atrial natriuretic peptide; hypertension; modeling; sympathetic nervous system

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