A structural constitutive model considering angular dispersion and waviness of collagen fibres of rabbit facial veins.

BACKGROUND: Structural constitutive models of vascular wall integrate information on composition and structural arrangements of tissue. In blood vessels, collagen fibres are arranged in coiled and wavy bundles and the individual collagen fibres have a deviation from their mean orientation. A complete structural constitutive model for vascular wall should incorporate both waviness and orientational distribution of fibres. We have previously developed a model, for passive properties of vascular wall, which considers the waviness of collagen fibres. However, to our knowledge there is no structural model of vascular wall which integrates both these features. METHODS: In this study, we have suggested a structural strain energy function that incorporates not only the waviness but also the angular dispersion of fibres. We studied the effect of parameters related to the orientational distribution on macro-mechanical behaviour of tissue during inflation-extension tests. The model was further applied on experimental data from rabbit facial veins. RESULTS: Our parametric study showed that the model is less sensitive to the orientational dispersion when fibres are mainly oriented circumferentially. The macro-mechanical response is less sensitive to changes in the mean orientation when fibres are more dispersed. The model accurately fitted the experimental data of veins, while not improving the quality of the fit compared to the model without dispersion. Our results showed that the orientational dispersion of collagen fibres could be compensated by a less abrupt and shifted to higher strain collagen engagement pattern. This should be considered when the model is fitted to experimental data and model parameters are used to study structural modifications of collagen fibre network in physiology and disease. CONCLUSIONS: The presented model incorporates structural features related to waviness and orientational distribution of collagen fibres and thus offers possibilities to better understand the relation between structure and function in the vascular wall. Also, the model can be used to further study mechanically induced collagen remodelling in vascular tissue in health and disease.

Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension.

AIMS: Growing evidence suggests that arginase misregulation plays a key role in the pathophysiology of essential hypertension. In the present study, we investigated the potential cardiovascular therapeutic effects of a long-term treatment with an arginase inhibitor in adult spontaneously hypertensive rats (SHR) with fully developed hypertension. METHODS AND RESULTS: Treatment of 25-week-old SHR with the arginase inhibitor N(omega)-hydroxy-nor-L-arginine (nor-NOHA, 40 mg/day for 10 weeks) sustainably reduced systolic blood pressure (-30 mmHg, P < 0.05). The antihypertensive effect of nor-NOHA was associated with changes on mesenteric artery reactivity including the restoration of angiotensin-II-induced contraction and acetylcholine-induced vasodilation to the values of normotensive Wistar Kyoto rats. Both nitric oxide synthase and cyclooxygenase-dependent mechanisms account for the improvement of endothelial function afforded by the arginase inhibitor, which in addition blunted hypertension-induced endothelial arginase I overexpression in mesenteric arteries. Nor-NOHA also prevented the remodelling of aorta as measured by collagen content and media/lumen ratio, and improved the compliance of carotid artery in SHR. Cardiac fibrosis assessed by collagen content of left heart ventricle was reduced by nor-NOHA, with no significant effect on cardiac hypertrophy. CONCLUSION: Our results report that a long-term treatment with an arginase inhibitor reduced blood pressure, improved vascular function, and reduced cardiac fibrosis in SHR with fully developed hypertension. These data suggest that arginase represents a promising novel target for pharmacological intervention in essential hypertension.

A structural model of the venous wall considering elastin anisotropy.

The three-dimensional biomechanical behavior of the vascular wall is best described by means of strain energy functions. Significant effort has been devoted lately in the development of structure-based models of the vascular wall, which account for the individual contribution of each major structural component (elastin, collagen, and vascular smooth muscle). However, none of the currently proposed structural models succeeded in simultaneously and accurately describing both the pressure-radius and pressure-longitudinal force curves. We have hypothesized that shortcomings of the current models are, in part, due to unaccounted anisotropic properties of elastin. We extended our previously developed biomechanical model to account for elastin anisotropy. The experimental data were obtained from inflation-extension tests on facial veins of five young white New Zealand rabbits. Tests have been carried out under a fully relaxed state of smooth muscle cells for longitudinal stretch ratios ranging from 100% to 130% of the in vivo length. The experimental data (pressure-radius, pressure-force, and zero-stress-state geometries) provided a complete biaxial mechanical characterization of rabbit facial vein and served as the basis for validating the applicability and accuracy of the new biomechanical model of the venous wall. When only the pressure-radius curves were fitted, both the anisotropic and the isotropic models gave excellent results. However, when both pressure-radius and pressure-force curves are simultaneously fitted, the model with isotropic elastin shows an average weighted residual sum of squares of 8.94 and 23.9 in the outer radius and axial force, respectively, as compared to averages of 6.07 and 4.00, when anisotropic elastin is considered. Both the Alkaike information criterion and Schwartz criterion show that the model with the anisotropic elastin is more successful in predicting the data for a wide range of longitudinal stretch ratios. We conclude that anisotropic description of elastin is required for a full 3D characterization of the biomechanics of the venous wall.