Blood pressure-induced physiological strain variability modulates wall structure and function in aorta rings.

Unlabelled: Vascular smooth muscle cells respond to mechanical stretch by reorganizing their cytoskeletal and contractile elements. Recently, we showed that contractile forces in rat aorta rings were maintained when the rings were exposed to 4 h of physiological variability in cycle-by-cycle strain, called variable stretch (VS), mimicking beat-to-beat blood pressure variability. Contractility, however, was reduced when the aorta was exposed to monotonous stretch (MS) with an amplitude equal to the mean peak strain of VS.

Objective: Here we reanalyzed the data to obtain wall stiffness as well as added new histologic and inhibitor studies to test the effects of VS on the extracellular matrix.

Main Results: The results demonstrate that while the stiffness of the aorta did not change during 4 h MS or VS, nonlinearity in mechanical behavior was slightly stronger following MS. The inhibitor studies also showed that mitochondrial energy production and cytoskeletal organization were involved in this fluctuation-driven mechanotransduction. Reorganization of β-actin in the smooth muscle layer quantified from immunohistochemically labeled images correlated with contractile forces during contraction. Histologic analysis of wall structure provided evidence of reorganization of elastin and collagen fibers following MS but less so following VS. The results suggested that the loss of muscle contraction in MS was compensated by reorganization of fiber structure leading to similar wall stiffness as in VS.

Significance: We conclude that muscle tone modulated by variability in stretch plays a role in maintaining aortic wall structural and mechanical homeostasis with implications for vascular conditions characterized by a loss or an increase in blood pressure variability.