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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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Time-averaged diameter (A) and intracellular calcium, determined from the fura ratio (B), as function of the distending pressure. Closed squares: during active tone and vasomotion induced by TEA and BayK8644. Open squares: under fully dilated conditions. *P < 0.05, dilated versus active tone (paired t-tests). Statistics between pressure levels are repeated measures ANOVA and Bonferroni post-hoc tests. Error bars are SEM, n= 9 vessels.
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fig01: Time-averaged diameter (A) and intracellular calcium, determined from the fura ratio (B), as function of the distending pressure. Closed squares: during active tone and vasomotion induced by TEA and BayK8644. Open squares: under fully dilated conditions. *P < 0.05, dilated versus active tone (paired t-tests). Statistics between pressure levels are repeated measures ANOVA and Bonferroni post-hoc tests. Error bars are SEM, n= 9 vessels.

Mentions: Figure 1 plots the time-averaged diameter and calcium levels as functions of the distending pressure in the presence of 1 μM BayK 8644 and 1 mM TEA (filled symbols). These averages were determined over the period between 5 and 15 min after each pressure step. For reference, the available values under full dilation are also indicated (open symbols). The combined addition of the calcium agonist and potassium channel blocker resulted in an initial deep constriction (not shown) followed by a very shallow, though significant constriction. Increasing the pressure induced a significant distension of the vessel, while myogenic responses were absent. At 17 mmHg, the time-averaged calcium signal was not significantly higher in the presence as compared to the absence of both drugs (Fig. 1B). Increasing the pressure in the presence of TEA and BayK 8644 resulted in a significant rise of calcium between 17 and 57 mmHg.


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)

Time-averaged diameter (A) and intracellular calcium, determined from the fura ratio (B), as function of the distending pressure. Closed squares: during active tone and vasomotion induced by TEA and BayK8644. Open squares: under fully dilated conditions. *P < 0.05, dilated versus active tone (paired t-tests). Statistics between pressure levels are repeated measures ANOVA and Bonferroni post-hoc tests. Error bars are SEM, n= 9 vessels.
© Copyright Policy
Related In: Results  -  Collection

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

fig01: Time-averaged diameter (A) and intracellular calcium, determined from the fura ratio (B), as function of the distending pressure. Closed squares: during active tone and vasomotion induced by TEA and BayK8644. Open squares: under fully dilated conditions. *P < 0.05, dilated versus active tone (paired t-tests). Statistics between pressure levels are repeated measures ANOVA and Bonferroni post-hoc tests. Error bars are SEM, n= 9 vessels.
Mentions: Figure 1 plots the time-averaged diameter and calcium levels as functions of the distending pressure in the presence of 1 μM BayK 8644 and 1 mM TEA (filled symbols). These averages were determined over the period between 5 and 15 min after each pressure step. For reference, the available values under full dilation are also indicated (open symbols). The combined addition of the calcium agonist and potassium channel blocker resulted in an initial deep constriction (not shown) followed by a very shallow, though significant constriction. Increasing the pressure induced a significant distension of the vessel, while myogenic responses were absent. At 17 mmHg, the time-averaged calcium signal was not significantly higher in the presence as compared to the absence of both drugs (Fig. 1B). Increasing the pressure in the presence of TEA and BayK 8644 resulted in a significant rise of calcium between 17 and 57 mmHg.

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