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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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Load line analysis of vasomotion. Data were separately analyzed for selected periods of regular calcium oscillations with 1–3 spikes in each oscillation. During such oscillations, various degrees of feedback were applied, as was shown by the example of Figure 7. Points on the horizontal axis denote isobaric vasomotion, points closer to the vertical axis indicate more isometric vasomotion. For each feedback level, diameter and pressure amplitude were determined, and their relation was determined by linear regression over the various feedback levels. Symbols are defined in panel C, the numbers are vessel numbers.
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fig08: Load line analysis of vasomotion. Data were separately analyzed for selected periods of regular calcium oscillations with 1–3 spikes in each oscillation. During such oscillations, various degrees of feedback were applied, as was shown by the example of Figure 7. Points on the horizontal axis denote isobaric vasomotion, points closer to the vertical axis indicate more isometric vasomotion. For each feedback level, diameter and pressure amplitude were determined, and their relation was determined by linear regression over the various feedback levels. Symbols are defined in panel C, the numbers are vessel numbers.

Mentions: Figure 8 plots diameter and pressure amplitudes during non-isobaric loading. The data on the diameter axes reflect isobaric vasomotion (no feedback) at the given baseline pressures, while data points closer to the upper ends of the regression line were obtained during higher feedback gains. The slopes of these lines, in analogy to cardiac muscle, reflect elastance of the activated SMC. Extrapolated intercepts with the pressure axis reflect the amplitude of pressure oscillations during completely isometric loading. These pressure oscillations are proportional to isometric active tension development and thus indicate contractile activation (see discussion). The data in Figure 8 are from four vessels, where episodes with single, double and triple spikes, where available, are separately analyzed. This way, 5–7 curves were obtained for each pressure. For a given baseline pressure, the slopes of the regression lines were similar for single and multiple spiking. For the three baseline pressures, these slopes averaged 3.95±1.77 (n= 5), 6.48±2.45 (n= 7) and 21.4±8.7 (n= 6) mmHg/% diameter change at respectively 17, 57 and 98 mmHg (P<0.001, 98 versus 17 and 57 mmHg). For the three experiments with single calcium spikes, the extrapolated intercept with the pressure axis (reflecting true isometric loading) averaged 38, 47 and 44 mmHg at respectively 17, 57 and 98 mmHg basal pressure. The experiments with double spikes had extrapolated isometric pressure oscillations averaging 67 (n= 1), 61 (n= 3) and 66 (n= 2) mmHg at the three basal pressure levels. The intercept was significantly higher for multiple spikes (P<0.01, 1 versus 2 and 3 spikes, GLM), but did not depend on the baseline pressure (P= NS).


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)

Load line analysis of vasomotion. Data were separately analyzed for selected periods of regular calcium oscillations with 1–3 spikes in each oscillation. During such oscillations, various degrees of feedback were applied, as was shown by the example of Figure 7. Points on the horizontal axis denote isobaric vasomotion, points closer to the vertical axis indicate more isometric vasomotion. For each feedback level, diameter and pressure amplitude were determined, and their relation was determined by linear regression over the various feedback levels. Symbols are defined in panel C, the numbers are vessel numbers.
© Copyright Policy
Related In: Results  -  Collection

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

fig08: Load line analysis of vasomotion. Data were separately analyzed for selected periods of regular calcium oscillations with 1–3 spikes in each oscillation. During such oscillations, various degrees of feedback were applied, as was shown by the example of Figure 7. Points on the horizontal axis denote isobaric vasomotion, points closer to the vertical axis indicate more isometric vasomotion. For each feedback level, diameter and pressure amplitude were determined, and their relation was determined by linear regression over the various feedback levels. Symbols are defined in panel C, the numbers are vessel numbers.
Mentions: Figure 8 plots diameter and pressure amplitudes during non-isobaric loading. The data on the diameter axes reflect isobaric vasomotion (no feedback) at the given baseline pressures, while data points closer to the upper ends of the regression line were obtained during higher feedback gains. The slopes of these lines, in analogy to cardiac muscle, reflect elastance of the activated SMC. Extrapolated intercepts with the pressure axis reflect the amplitude of pressure oscillations during completely isometric loading. These pressure oscillations are proportional to isometric active tension development and thus indicate contractile activation (see discussion). The data in Figure 8 are from four vessels, where episodes with single, double and triple spikes, where available, are separately analyzed. This way, 5–7 curves were obtained for each pressure. For a given baseline pressure, the slopes of the regression lines were similar for single and multiple spiking. For the three baseline pressures, these slopes averaged 3.95±1.77 (n= 5), 6.48±2.45 (n= 7) and 21.4±8.7 (n= 6) mmHg/% diameter change at respectively 17, 57 and 98 mmHg (P<0.001, 98 versus 17 and 57 mmHg). For the three experiments with single calcium spikes, the extrapolated intercept with the pressure axis (reflecting true isometric loading) averaged 38, 47 and 44 mmHg at respectively 17, 57 and 98 mmHg basal pressure. The experiments with double spikes had extrapolated isometric pressure oscillations averaging 67 (n= 1), 61 (n= 3) and 66 (n= 2) mmHg at the three basal pressure levels. The intercept was significantly higher for multiple spikes (P<0.01, 1 versus 2 and 3 spikes, GLM), but did not depend on the baseline pressure (P= NS).

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