Functional rationalization of actin cytoskeletal dynamics in the genesis of myogenic tone

The myogenic response is the autoregulatory vasoconstriction to elevated intraluminal pressure, which underlies hemodynamic control in the cerebral and peripheral vasculature. While “net” myosin light chain phosphorylation is key to its initiation, functional changes to the actin cytoskeleton may also play a role. Study Objective: Elucidate the role of actin cytoskeletal recruitment to myogenic tone development in mouse mesentery arteries. Hypothesis: Defined patterns of intraluminal pressurization can functionally elucidate how cytoskeletal/vascular remodelling sets basal tone development. Methods: Third-order mouse mesenteric resistance arteries mounted in a myograph were exposed to a range of pressure profiles while the rate and magnitude of tone development were quantified in the absence/presence of Latrunculin A (5 µM). Data and Results: Arteries were first exposed to two sequential pressurizations (from 15 to 100 mmHg, 60-minute separation), with myogenic tone developing markedly quicker on the second pressurization. Latrunculin A, a G-actin capping agent that prevents new F-actin formation, had no impact on established myogenicity when applied after tone development following the second pressurization. However, when applied prior to the first 100mmHg pressurization, it markedly attenuated tone development. With regard to the former, tone development persisted in the presence of Latrunculin A applied prior to the second 100 mmHg pressurization; however, its attenuation, resulting in vasodilation, varied in accordance with the time interval (15, 60, and 120 minutes) separating the sequential pressurizations. From these observations, a functional rate of actin cytoskeletal polymerization/depolymerization was calculated, the former notably quicker than the latter. Western blots were subsequently performed to quantitate the G-actin content in mesenteric resistance arteries; its disappearance with pressurization aligned with our functional work in support of our overarching hypothesis. Conclusions: This study highlights the plasticity of the actin cytoskeleton in setting myogenic tone, the rate dynamics of polymerization/depolymerization being distinct from the rapid Ca 2+ response driving myosin light chain phosphorylation. The fundamental insight generated herein fosters deeper consideration of “vascular dysfunction” and how to rationally expand the therapeutic window to the treatment of hypertension, diabetes, and arterial vasospasm. Supported by NSERC and the Roraback Chair in Vascular Biology and Neuroscience. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.