Susanne Ditlevsen
Københavns universitet


Title:

Parameter estimation in a stochastic model of the tubuloglomerular
feedback mechanism in a rat nephron: differences between spontaneously
hypertensive rats and Sprague-Dawley rats


Abstract:

Experimental studies have demonstrated the presence of self-sustained
oscillations in proximal tubular pressure in the nephrons of rats. The
oscillations are regular in normotensive Sprague-Dawley rats, and
highly irregular in spontaneously hypertensive rats.

A dynamic model of the renal autoregulation has been extended to
include a stochastic differential equations model of one of the main
parameters that determines feedback gain. The model reproduces
fluctuations and irregularities in both period and amplitude that the
former deterministic models failed to describe. This approach assumes
that the gain exhibits spontaneous erratic variations, which can be
explained by a variety of influences, which change over time (blood
pressure, hormone levels etc).

Estimation of key parameters of the model reveals important
differences in the autoregulation mechanisms between the two strains
of rats. This insight was achieved by directly modeling the dynamic
features of the feedback gain, normally modeled with a constant that
is not capable of capturing time variations.