Vascular smooth muscle cells (VSMCs) can regulate arterial mechanics via contractile activity in response to changing mechanical and chemical signals. Contractility is traditionally evaluated via uniaxial isometric testing of isolated rings despite the in vivo environment being very different. Most blood vessels maintain a locally preferred value of in vivo axial stretch while subjected to changes in distending pressure, but both of these phenomena are obscured in uniaxial isometric testing. Few studies have rigorously analyzed the role of in vivo loading conditions in smooth muscle function. Thus, we evaluated effects of uniaxial versus biaxial deformations on smooth muscle contractility by stimulating two regions of the mouse aorta with different vasoconstrictors using one of three testing protocols: (i) uniaxial isometric testing, (ii) biaxial isometric testing, and (iii) axially isometric plus isobaric testing. Comparison of methods (i) and (ii) revealed increased sensitivity and contractile capacity to potassium chloride and phenylephrine (PE) with biaxial isometric testing, and comparison of methods (ii) and (iii) revealed a further increase in contractile capacity with isometric plus isobaric testing. Importantly, regional differences in estimated in vivo axial stretch suggest locally distinct optimal biaxial configurations for achieving maximal smooth muscle contraction, which can only be revealed with biaxial testing. Such differences highlight the importance of considering in vivo loading and geometric configurations when evaluating smooth muscle function. Given the physiologic relevance of axial extension and luminal pressurization, we submit that, when possible, axially isometric plus isobaric testing should be employed to evaluate vascular smooth muscle contractile function.
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March 2019
Research-Article
Fundamental Roles of Axial Stretch in Isometric and Isobaric Evaluations of Vascular Contractility
Alexander W. Caulk,
Alexander W. Caulk
Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520
Yale University,
New Haven, CT 06520
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Jay D. Humphrey,
Jay D. Humphrey
Fellow ASME
Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520;
Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520;
Vascular Biology and Therapeutics Program,
Yale University,
New Haven, CT 06520
Yale University,
New Haven, CT 06520
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Sae-Il Murtada
Sae-Il Murtada
Department of Biomedical Engineering,
Yale University,
55 Prospect Street,
New Haven, CT 06520
e-mail: sae-il.murtada@yale.edu
Yale University,
55 Prospect Street,
New Haven, CT 06520
e-mail: sae-il.murtada@yale.edu
Search for other works by this author on:
Alexander W. Caulk
Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520
Yale University,
New Haven, CT 06520
Jay D. Humphrey
Fellow ASME
Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520;
Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520;
Vascular Biology and Therapeutics Program,
Yale University,
New Haven, CT 06520
Yale University,
New Haven, CT 06520
Sae-Il Murtada
Department of Biomedical Engineering,
Yale University,
55 Prospect Street,
New Haven, CT 06520
e-mail: sae-il.murtada@yale.edu
Yale University,
55 Prospect Street,
New Haven, CT 06520
e-mail: sae-il.murtada@yale.edu
1Corresponding author.
Manuscript received April 10, 2018; final manuscript received November 13, 2018; published online January 25, 2019. Assoc. Editor: Jonathan Vande Geest.
J Biomech Eng. Mar 2019, 141(3): 031008 (10 pages)
Published Online: January 25, 2019
Article history
Received:
April 10, 2018
Revised:
November 13, 2018
Citation
Caulk, A. W., Humphrey, J. D., and Murtada, S. (January 25, 2019). "Fundamental Roles of Axial Stretch in Isometric and Isobaric Evaluations of Vascular Contractility." ASME. J Biomech Eng. March 2019; 141(3): 031008. https://doi.org/10.1115/1.4042171
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