title: Modelling the vascular response to sympathetic postganglionic nerve activity.
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.
authors.affiliation: School of Physiology & Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol BS8 1TD, UK; Department of Engineering Mathematics, Merchant Venturers Building, Woodland Road, University of Bristol, Bristol BS8 1UB, UK.
authors.forename: Linford J B
authors.initials: LJ
authors.lastname: Briant
authors.affiliation: School of Physiology & Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.affiliation: School of Physiology & Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol BS8 1TD, UK; Department of Anaesthesia, University Hospitals Bristol, Bristol BS2 8HW, UK.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pickering
authors.affiliation: Department of Engineering Mathematics, Merchant Venturers Building, Woodland Road, University of Bristol, Bristol BS8 1UB, UK. Electronic address: A.R.Champneys@Bristol.ac.uk.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Champneys
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008955:Models, Cardiovascular; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011918:Rats, Inbred SHR; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D015544:Inositol 1,4,5-Trisphosphate; D019204:GTP-Binding Proteins; D002118:Calcium; D009638:Norepinephrine
keywords: Bursting; Calcium dynamics; Hypertension; Neurone dynamics; Sympathetic nervous system