The kidney has long been known as an organ of homeostasis,
which has been taken to imply that the steady state is the most
appropriate condition in which to view the kidney. However,
the kidney has an intrinsic rhythm (Holstein-Rathlou and
Leyssac, 1987; Holstein-Rathlou and Marsh, 1989), and it is
known that disorders of these rhythms are associated with at
least some cardiovascular diseases, such as renovascular
hypertension (Yip et al. 1991), and in spontaneous
hypertension in rats (Wagner et al. 1997). Renal blood flow
(RBF) and pressure mechanisms have been modelled using a
range of dynamic system models (Holstein-Rathlou and Marsh,
1994b). This has improved our understanding of the
controlling mechanisms, enabling the evaluation of models,
and has been of use in determining the relative importance of
various inputs in the control of RBF. However, in a
comprehensive review paper, Holstein-Rathlou and Marsh
(1994b) reveal that, even using a combination of the best
existing modelling approaches, there are some significant
discrepancies between the predictions of such models and the
actual behaviour of the kidney. One explanation for this may
be that previous work has given no consideration to the
importance of sympathetic nerve activity (SNA) in regulating
RBF.
Historically, it has been hypothesised that small variations
in SNA occurring during normal daily events play little role
in modulating renal blood flow RBF (Dibona and Kopp,
1997). This suggests that RBF, under basal conditions, is
likely to be regulated by other factors such as arterial
pressure, hormones and autoregulation. This hypothesis has
been supported by a number of studies in both anaesthetised
and conscious animals, in which RBF was generally
estimated by the clearance of a substance across the kidney,
and nerve activity increased and decreased in response to
afferent stimuli (Hesse and Johns, 1984; Miki et al. 1989a,b).
However, this approach does not take into account that SNA
is an inherently dynamic signal, responding rapidly to
3425 The Journal of Experimental Biology 201, 3425–3430 (1998)
Printed in Great Britain © The Company of Biologists Limited 1998
JEB1726
A linear autoregressive/moving-average model was
developed to describe the dynamic relationship between
mean arterial pressure (MAP), renal sympathetic nerve
activity (SNA) and renal blood flow (RBF) in conscious
rabbits. The RBF and SNA to the same kidney were
measured under resting conditions in a group of eight
rabbits. Spectral analysis of the data sampled at
0.4 Hz showed that the low-pass bandwidth of the signal
power for RBF was approximately 0.05 Hz. An
autoregressive/moving-average model with an exogenous
input (ARMAX) was then derived (using the iterative
Gauss–Newton algorithm provided by the MATLAB
identification Toolbox), with MAP and SNA as inputs and
RBF as output, to model the low-frequency fluctuations.
The model step responses of RBF to changes in SNA and
arterial pressure indicated an overdamped response with a
settling time that was usually less than 2 s. Calculated
residuals from the model indicated that 79±5 % (mean ±
S.D., averaged over eight independent experiments) of the
variation in RBF could be accounted for by the variations
in arterial pressure and SNA. Two additional single-input
models for each of the inputs were similarly obtained and
showed conclusively that changes in RBF, in the conscious
resting rabbit, are a function of both SNA and MAP and
that the SNA signal has the predominant effect. These
results indicate a strong reliance on SNA for the dynamic
regulation of RBF. Such information is likely to be
important in understanding the diminished renal function
that occurs in a variety of disease conditions in which
overactivity of the sympathetic nervous system occurs.
Key words: mathematical model, ARMAX, spectral analysis, arterial
pressure, blood flow, sympathetic nerve activity, rabbit.
Summary
Introduction
MODELLING OF THE DYNAMIC RELATIONSHIP BETWEEN ARTERIAL PRESSURE,
RENAL SYMPATHETIC NERVE ACTIVITY AND RENAL BLOOD FLOW IN
CONSCIOUS RABBITS
CLIVE S. BERGER
1
AND SIMON C. MALPAS
1,2,
*
1
Department of Electrical Engineering and Computer Systems, Monash University, Clayton, Baker Medical Research
Institute, Prahran, Victoria, Australia and
2
Department of Physiology, University of Auckland, PO Box 9201, New
Zealand
*Author for correspondence at address 2 (e-mail; s.malpas@auckland.ac.nz)
Accepted 5 October; published on WWW 17 November 1998