Differences in transmural pressure and axial loading ex vivo affect arterial remodeling and material properties.

Arterial axial strains, present in the in vivo environment, often become reduced due to either bypass grafting or the normal aging process. Since the prevalence of hypertension increases with aging, arteries are often exposed to both decreased axial stretch and increased transmural pressure. The combined effects of these mechanical stimuli on the mechanical properties of vessels have not previously been determined. Porcine carotid arteries were cultured for 9 days at normal and reduced axial stretch ratios in the presence of normotensive and hypertensive transmural pressures using ex vivo perfusion techniques. Measurements of the amount of axial stress were obtained through longitudinal tension tests while inflation-deflation test results were used to determine circumferential stresses and incremental moduli. Macroscopic changes in artery geometry and zero-stress state opening angles were measured. Arteries cultured ex vivo remodeled in response to the mechanical environment, resulting in changes in arterial dimensions of up to approximately 25% and changes in zero-stress opening angles of up to approximately 55 degrees . While pressure primarily affected circumferential remodeling and axial stretch primarily affected axial remodeling, there were clear examples of interactions between these mechanical stimuli. Culture with hypertensive pressure, especially when coupled with reduced axial loading, resulted in a rightward shift in the pressure-diameter relationship relative to arteries cultured with normotensive pressure. The observed differences in the pressure-diameter curves for cultured arteries were due to changes in artery geometry and, in some cases, changes in the arteries' intrinsic mechanical properties. Relative to freshly isolated arteries, arteries cultured under mechanical conditions similar to in vivo conditions were stiffer, suggesting that aspects of the ex vivo culture other than the mechanical environment also influenced changes in the arteries' mechanical properties. These results confirm the well-known importance of transmural pressure with regard to arterial wall mechanics while highlighting additional roles for axial stretch in determining mechanical behavior.

Transmural pressure and axial loading interactively regulate arterial remodeling ex vivo.

Physiological axial strains range between 40 and 60% in arteries, resulting in stresses comparable to those due to normal blood pressure or flow. To investigate the contribution of axial strain to arterial remodeling and function, porcine carotid arteries were cultured for 9 days at physiological and reduced axial stretch ratios in the presence of normotensive and hypertensive transmural pressures by ex vivo perfusion techniques. Consistent with previous in vivo studies, vessels cultured with physiological levels of axial strain and exposed to hypertensive pressure had greater mass, wall area, and outer diameter relative to those cultured at the same axial stretch ratio and normotensive pressure. Reducing the amount of axial strain resulted in mass loss and decreased cell proliferation. Culture in a hypertensive pressure environment at reduced axial strain produced arteries with greater contractility in response to norepinephrine. Arteries cultured at reduced axial strain with the matrix metalloproteinase inhibitor GM6001 maintained their masses over culture, indicating a possible mechanism for this model of axial stretch-dependent remodeling. Although not historically considered one of the primary stimuli for remodeling, multiple linear regression analysis revealed that axial strain had an impact similar to or greater than transmural pressure on various remodeling indexes (i.e., outer diameter, wall area, and wet mass), suggesting that axial strain is a primary mediator of vascular remodeling.