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Vasomotion dynamics following calcium spiking depend on both cell signalling and limited constriction velocity in rat mesenteric small arteries.

VanBavel E, van der Meulen ET, Spaan JA - J. Cell. Mol. Med. (2008)

Bottom Line: The dirac impulse response of this model had an amplitude that was strongly reduced with increasing perfusion pressure between 17 and 98 mmHg, while time to peak and relaxation time were the largest at an intermediate pressure (57 mmHg: respectively 0.9 and 2.3 sec).In conclusion, this study demonstrates the feasibility of quantitating calcium-activation dynamics in vasomoting small arteries.Performing such analyses during pharmacological intervention and in genetic models provides a tool for unravelling calcium-contraction coupling in small arteries.

View Article: PubMed Central - PubMed

Affiliation: Academic Medical Center, University of Amsterdam, Department of Medical Physics, Amsterdam, The Netherlands. e.vanbavel@amc.uva.nl

ABSTRACT
Vascular smooth muscle cell contraction depends on intracellular calcium. However, calcium-contraction coupling involves a complex array of intracellular processes. Quantitating the dynamical relation between calcium perturbations and resulting changes in tone may help identifying these processes. We hypothesized that in small arteries accurate quantitation can be achieved during rhythmic vasomotion, and questioned whether these dynamics depend on intracellular signalling or physical vasoconstriction. We studied calcium-constriction dynamics in cannulated and pressurized rat mesenteric small arteries ( approximately 300 microm in diameter). Combined application of tetra-ethyl ammonium (TEA) and BayK8644 induced rhythmicity, consisting of regular and irregular calcium spiking and superposition of spikes. Calcium spikes induced delayed vasomotion cycles. Their dynamic relation could be fitted by a linear second-order model. The dirac impulse response of this model had an amplitude that was strongly reduced with increasing perfusion pressure between 17 and 98 mmHg, while time to peak and relaxation time were the largest at an intermediate pressure (57 mmHg: respectively 0.9 and 2.3 sec). To address to what extent these dynamics reside in intracellular signalling or vasoconstriction, we applied rhythmic increases in pressure counteracting the vasoconstriction. This revealed that calcium-activation coupling became faster when vasoconstriction was counteracted. During such compensation, a calcium impulse response remained that lasted 0.5 sec to peak activation, followed by a 1.0 sec relaxation time, attributable to signalling dynamics. In conclusion, this study demonstrates the feasibility of quantitating calcium-activation dynamics in vasomoting small arteries. These dynamics relate to both intracellular signalling and actual vasoconstriction. Performing such analyses during pharmacological intervention and in genetic models provides a tool for unravelling calcium-contraction coupling in small arteries.

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Dirac pulse parameters for the second-order model (see Fig. 5) during proportional feedback, for a baseline pressure of 17 mmHg (A–C) and 57 mmHg (D–F). Individual symbols are separate experiments.
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fig10: Dirac pulse parameters for the second-order model (see Fig. 5) during proportional feedback, for a baseline pressure of 17 mmHg (A–C) and 57 mmHg (D–F). Individual symbols are separate experiments.

Mentions: In order to present meaningful averages of peak activation times during non-isobaric loading despite the variable calcium waveforms between the experiments, we again fitted the second-order model and derived impulse response characteristics. This was done only for basal pressures of 17 and 57 mmHg, since at 98 mmHg during feedback the amplitude of the diameter signal was very low, resulting in a poor signal to noise ratio. Figure 10 plots the amplitude, peak time and relaxation time for both baseline pressures as a function of the feedback gain (n= 4). As expected, diameter amplitude of the impulse response (Fig. 10A–D) decreased strongly for higher feedback gains. At the lower pressure, both the peak time and relaxation time decreased slightly with more isometric loading (Fig. 10B–C), while at 57 mmHg baseline pressure, the initial peak time and relaxation times were higher, and the reduction with more isometric loading was larger (Fig. 10E–F). The reductions of not only amplitude, but also peak time and relaxation time at higher feedback gain were significant, both at 17 and 57 mmHg (GLM using dependence on experiment and linear regression with gain, P<0.005 for all tests). Thus, the impulse response became shorter at more isometric loading.


Vasomotion dynamics following calcium spiking depend on both cell signalling and limited constriction velocity in rat mesenteric small arteries.

VanBavel E, van der Meulen ET, Spaan JA - J. Cell. Mol. Med. (2008)

Dirac pulse parameters for the second-order model (see Fig. 5) during proportional feedback, for a baseline pressure of 17 mmHg (A–C) and 57 mmHg (D–F). Individual symbols are separate experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401133&req=5

fig10: Dirac pulse parameters for the second-order model (see Fig. 5) during proportional feedback, for a baseline pressure of 17 mmHg (A–C) and 57 mmHg (D–F). Individual symbols are separate experiments.
Mentions: In order to present meaningful averages of peak activation times during non-isobaric loading despite the variable calcium waveforms between the experiments, we again fitted the second-order model and derived impulse response characteristics. This was done only for basal pressures of 17 and 57 mmHg, since at 98 mmHg during feedback the amplitude of the diameter signal was very low, resulting in a poor signal to noise ratio. Figure 10 plots the amplitude, peak time and relaxation time for both baseline pressures as a function of the feedback gain (n= 4). As expected, diameter amplitude of the impulse response (Fig. 10A–D) decreased strongly for higher feedback gains. At the lower pressure, both the peak time and relaxation time decreased slightly with more isometric loading (Fig. 10B–C), while at 57 mmHg baseline pressure, the initial peak time and relaxation times were higher, and the reduction with more isometric loading was larger (Fig. 10E–F). The reductions of not only amplitude, but also peak time and relaxation time at higher feedback gain were significant, both at 17 and 57 mmHg (GLM using dependence on experiment and linear regression with gain, P<0.005 for all tests). Thus, the impulse response became shorter at more isometric loading.

Bottom Line: The dirac impulse response of this model had an amplitude that was strongly reduced with increasing perfusion pressure between 17 and 98 mmHg, while time to peak and relaxation time were the largest at an intermediate pressure (57 mmHg: respectively 0.9 and 2.3 sec).In conclusion, this study demonstrates the feasibility of quantitating calcium-activation dynamics in vasomoting small arteries.Performing such analyses during pharmacological intervention and in genetic models provides a tool for unravelling calcium-contraction coupling in small arteries.

View Article: PubMed Central - PubMed

Affiliation: Academic Medical Center, University of Amsterdam, Department of Medical Physics, Amsterdam, The Netherlands. e.vanbavel@amc.uva.nl

ABSTRACT
Vascular smooth muscle cell contraction depends on intracellular calcium. However, calcium-contraction coupling involves a complex array of intracellular processes. Quantitating the dynamical relation between calcium perturbations and resulting changes in tone may help identifying these processes. We hypothesized that in small arteries accurate quantitation can be achieved during rhythmic vasomotion, and questioned whether these dynamics depend on intracellular signalling or physical vasoconstriction. We studied calcium-constriction dynamics in cannulated and pressurized rat mesenteric small arteries ( approximately 300 microm in diameter). Combined application of tetra-ethyl ammonium (TEA) and BayK8644 induced rhythmicity, consisting of regular and irregular calcium spiking and superposition of spikes. Calcium spikes induced delayed vasomotion cycles. Their dynamic relation could be fitted by a linear second-order model. The dirac impulse response of this model had an amplitude that was strongly reduced with increasing perfusion pressure between 17 and 98 mmHg, while time to peak and relaxation time were the largest at an intermediate pressure (57 mmHg: respectively 0.9 and 2.3 sec). To address to what extent these dynamics reside in intracellular signalling or vasoconstriction, we applied rhythmic increases in pressure counteracting the vasoconstriction. This revealed that calcium-activation coupling became faster when vasoconstriction was counteracted. During such compensation, a calcium impulse response remained that lasted 0.5 sec to peak activation, followed by a 1.0 sec relaxation time, attributable to signalling dynamics. In conclusion, this study demonstrates the feasibility of quantitating calcium-activation dynamics in vasomoting small arteries. These dynamics relate to both intracellular signalling and actual vasoconstriction. Performing such analyses during pharmacological intervention and in genetic models provides a tool for unravelling calcium-contraction coupling in small arteries.

Show MeSH
Related in: MedlinePlus