Non-linear analysis and modelling of the cellular mechanisms that regulate arterial vasomotion

Griffith, T. M.; Parthimos, Dimitris; Edwards, David Hughes

doi:10.1243/095440605x16965

Cited by 4 publications

(2 citation statements)

References 93 publications

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“…The resilience of Ca 2+ dynamics under CPA was reproduced by the simulations. A noteworthy aspect of the function of CPA is its ability to transform arterial vasomotion in a controlled manner that follows hallmark transition routes out of chaotic behaviour [ 35 , 38 ]. Evidence of this behaviour is shown in figure 11 a , b although detailed investigation of nonlinear oscillatory transitions was not an aim of this work.…”

Section: Discussionmentioning

confidence: 99%

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics

Coccarelli

Edwards

Aggarwal

et al. 2018

J. R. Soc. Interface.

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Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase; and ryanodine, a diterpenoid that modulates Ca2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca2+ dynamics. Cytosolic Ca2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental observations qualitatively, as well as quantitatively within a range of physiological parametric values. The model also illustrated how increased intercellular coupling led to smooth muscle coordination and the genesis of vascular tone.

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Section: Discussionmentioning

confidence: 99%

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics

Coccarelli

Edwards

Aggarwal

et al. 2018

J. R. Soc. Interface.

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“…For example, there is increasing evidence that the internal system behaviour of Homo sapiens is of a chaotic (non-linear dynamic) manner. In this context see [42,43] relating to the cardiovascular system, in a journal special issue on Chaos published in March 2006.Also,Alzheimer's and Parkinson's diseases are being investigated along similar lines [44]. Such behaviour does not so much prove the above model, but rather that the model is consistent with current medical evidence.…”

Section: Introductionmentioning

confidence: 99%

The laws of thermodynamics and Homo sapiens the engineer

Collins

Stąsiek

Mikielewicz

2006

WIT Transactions on State-of-the-Art in Science and Engineering

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One of the key developments in the university scene since the publications of The Origin of Species has been the emergence of engineering as a discipline in its own right. Over the same timescale the realization has developed that the laws of thermodynamics, universal in their engineering scope, must also apply to biology and living systems. As a matter of historical fact, the relationship between biology and thermodynamics had a bad start, and the reasons for this are discussed. Now one of the foundation concepts for thermodynamics is that of the heat engine, stemming from the radical achievement of the Industrial Revolution of being able to produce mechanical work from heat. In this chapter, we find that by re-defining the heat engine in terms of output, all organisms can be viewed as 'survival engines', certain animal species and man as 'work engines', and man himself as a 'complexity engine'. A number of examples are taken from the process of building the dome of the cathedral at Florence by Brunelleschi, a defining moment in the history of the Renaissance. This interpretation of Homo sapiens is consistent with Lumsden and Wilson's assessment of man as being the only eucultural species: various consequences of this are discussed. The chapter completes our trilogy of studies on the laws of thermodynamics, by then focusing on the possibility of further laws for living organisms, especially Kauffman's proposal for a fourth law. Finally, a concluding discussion entitled 'How mathematical is biology?' highlights the question of including mathematics as part of that integration.

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Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses

Wit

Griffith

2010

Pflugers Arch - Eur J Physiol

134

141

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It is becoming increasingly evident that electrical signaling via gap junctions plays a central role in the physiological control of vascular tone via two related mechanisms (1) the endothelium-derived hyperpolarizing factor (EDHF) phenomenon, in which radial transmission of hyperpolarization from the endothelium to subjacent smooth muscle promotes relaxation, and (2) responses that propagate longitudinally, in which electrical signaling within the intimal and medial layers of the arteriolar wall orchestrates mechanical behavior over biologically large distances. In the EDHF phenomenon, the transmitted endothelial hyperpolarization is initiated by the activation of Ca(2+)-activated K(+) channels channels by InsP(3)-induced Ca(2+) release from the endoplasmic reticulum and/or store-operated Ca(2+) entry triggered by the depletion of such stores. Pharmacological inhibitors of direct cell-cell coupling may thus attenuate EDHF-type smooth muscle hyperpolarizations and relaxations, confirming the participation of electrotonic signaling via myoendothelial and homocellular smooth muscle gap junctions. In contrast to isolated vessels, surprisingly little experimental evidence argues in favor of myoendothelial coupling acting as the EDHF mechanism in arterioles in vivo. However, it now seems established that the endothelium plays the leading role in the spatial propagation of arteriolar responses and that these involve poorly understood regenerative mechanisms. The present review will focus on the complex interactions between the diverse cellular signaling mechanisms that contribute to these phenomena.

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Non-linear analysis and modelling of the cellular mechanisms that regulate arterial vasomotion

Cited by 4 publications

References 93 publications

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics

The laws of thermodynamics and Homo sapiens the engineer

Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses

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