Modelling the vascular response to sympathetic postganglionic nerve activity.

Linford J.B Briant,Alan R Champneys,Anthony E Pickering,Julian F.R Paton

doi:10.1016/j.jtbi.2015.01.037

Abstract

This paper explores the influence of burst properties of the sympathetic nervous system on arterial contractility. Specifically, a mathematical model is constructed of the pathway from action potential generation in a sympathetic postganglionic neurone to contraction of an arterial smooth muscle cell. The differential equation model is a synthesis of models of the individual physiological processes, and is shown to be consistent with physiological data.The model is found to be unresponsive to tonic (regular) stimulation at typical frequencies recorded in sympathetic efferents. However, when stimulated at the same average frequency, but with repetitive respiratory-modulated burst patterns, it produces marked contractions. Moreover, the contractile force produced is found to be highly dependent on the number of spikes in each burst. In particular, when the model is driven by preganglionic spike trains recorded from wild-type and spontaneously hypertensive rats (which have increased spiking during each burst) the contractile force was found to be 10-fold greater in the hypertensive case. An explanation is provided in terms of the summative increased release of noradrenaline. Furthermore, the results suggest the marked effect that hypertensive spike trains had on smooth muscle cell tone can provide a significant contribution to the pathology of hypertension.

Highlights

The contractile behaviour of smooth muscle cells (SMCs) in resistance arteries is known to be controlled by the sympathetic nervous system, whose activity exhibits bursting rhythms
Note that the simulations are for a single SMC, whereas the experimental data is for an arterial response
We found that SMCs are unresponsive to tonic stimulation at average firing frequencies typical of those reported in single sympathetic fibres (Habler et al, 1994), which highlights the importance of bursting

Summary

Introduction

The contractile behaviour of smooth muscle cells (SMCs) in resistance arteries is known to be controlled by the sympathetic nervous system, whose activity exhibits bursting rhythms. Cell contractions, causing vasoconstriction and increases in arterial blood pressure This activity, in both pre- and postganglionic neurones, is known to exhibit bursting that is entrained to the respiratory rhythm, due to central coupling with respiratory pattern generators (Habler et al, 1994). A quantification of how this bursting activity influences arterial smooth muscle cell contractility is important as changes to sympathetic bursting are characteristic of cardiovascular diseases, such as hypertension and heart failure. This sympathetic nerve activity is known to be elevated in the spontaneously hypertensive (SH) rat and to exhibit amplified sympathetic-respiratory coupling (Simms et al, 2009).

Results

Discussion

Conclusion