Calcium Dynamics and Vasomotion in Arteries Subject to Isometric, Isobaric, and Isotonic Conditions

Abstract

In vitro, different techniques are used to study the smooth muscle cells' calcium dynamics and contraction/relaxation mechanisms on arteries. Most experimental studies use either an isometric or an isobaric setup. However, in vivo, a blood vessel is neither isobaric nor isometric nor isotonic, as it is continuously submitted to intraluminal pressure variations arising from heart beat. We use a theoretical model of the smooth muscle calcium and arterial radius dynamics to determine whether results may be considerably different depending on the experimental conditions (isometric, isobaric, isotonic, or cyclic pressure variations). We show that isobaric conditions appear to be more realistic than isometric or isotonic situations, as the calcium dynamics is similar under cyclic intraluminal pressure variations (in vivo-like situation) and under a constant pressure (isobaric situation). The arterial contraction is less pronounced in isotonic than in isobaric conditions, and the vasoconstrictor sensitivity higher in isometric than isobaric or isotonic conditions, in agreement with experimental observations. Interestingly, the model predicts that isometric conditions may generate artifacts like the coexistence of multiple stable states. We have verified this model prediction experimentally using rat mesenteric arteries mounted on a wire myograph and stimulated with phenylephrine.

Renal Autoregulation in Health and Disease

“…This was dependent on RyR-mediated Ca 2ϩ mobilization and Ca 2ϩ entry through VOCCs (529,1525). Moreover, cyclic variations in BP in vivo modulated the arterial diameter and VSMC [Ca 2ϩ ] i (818,819).…”

Small Artery Remodeling: Current Concepts and Questions

“…Figure 2d (‘tone = 0’) shows the passive characteristics in a cannulated vessel. Ignoring finite wall thickness and axial distension, passive curves recorded using isometric and isobaric methods are roughly equivalent, and these curves can be converted into each other via the law of Laplace [58,59,60,61,62,63]. The passive vessels are characterized by an unloaded diameter and non-linear elasticity reflected by an increasing incremental elastic modulus at higher distensions.…”

Mechanical control of cation channels in the myogenic response

“…Since second messengers in the cytosol are thought to modulate the activation and inactivation of channels that facilitate an increased cytosolic Ca 2ϩ and contraction, the governing stimulus could be sensed by structures other than the channels themselves. This separation between mechanisms at the channel level and the overall governing mechanical stimulus are implied in recent theoretical studies in which activation of stretch-activated channels is actually formulated to respond proportionally to vessel wall stress (5,24,25,53). In all previous theoretical studies, model validation to represent the myogenic response is made only qualitatively, and comparison of different controlling mechanical stimuli and possible transduction pathways is not discussed.…”

“…Simulation protocols utilizing a depolarizing voltage pulse and applied strain were used to interrogate the model function with respect to qualitative and quantitative features from experimental studies of VSM cells. Koenigsberger et al (24,25) investigated the myogenic response and oscillatory behavior of microvessels known as vasomotion with a similar model but focused on the influence of stretch-activated channels that were formulated to be activated by stress in the vessel. VSM force generation based on cytosolic Ca 2ϩ levels is represented in these two models using the Hai and Murphy VSM cross-bridge model (14), and both have used a vessel wall mechanics model to show the microvessel constriction and dilation.…”