Paradoxically decreased aortic wall stiffness in response to vitamin D3-induced calcinosis. A biphasic analysis of segmental elastic properties in conscious dogs.

Abstract

We studied the aortic elastic behavior in response to vitamin D3-induced accelerated calcinosis in conscious dogs chronically instrumented with a pressure microtransducer and a pair of ultrasonic diameter dimension gauges in the upper descending thoracic aorta. The two functional phases of the elastic segmental properties of the aorta in vivo were discriminated by computation on a beat-by-beat basis from the phasic pressure-diameter (P-D) hysteresis loops in basal conditions and during the transient state of a wide range of pressures obtained mechanically (aortic occlusion) or pharmacologically (angiotensin bolus). The overall P-D curve formed by all P-D hysteresis loops was comprised of two linear relations according to a model that assumes that only elastin is stretched at lower pressures, whereas both elastin and collagen are stretched at higher pressures. The slope of the first linear portion of the P-D curve was considered as the elastin P-D elastic modulus, and the slope of the curve obtained by subtraction between the P-D curve and the extrapolation of the elastin straight line was assumed to be the collagen P-D elastic modulus. After vitamin D3-induced calcinosis, the elastin elastic modulus was unaffected, whereas the collagen elastic modulus decreased significantly during occlusion maneuvers (58.6%, p less than 0.01) and during bolus injections of angiotensin (37.2%, p less than 0.05). The collagen elastic modulus correlated with the serum calcium concentration (r = -0.65, p less than 0.001) and with the aortic pulse pressure (r = 0.51, p less than 0.01), and this relation persisted at constant heart rate. Histopathologic analysis evidenced calcium-depositing elastic lamina, focal disappearance of collagen, and rupture of elastic fibers. The present study shows that accelerated, severe, experimental calcinosis-inducing calcium deposition inside the large artery walls is accompanied by a clear-cut paradoxical reduction in arterial rigidity that is mainly due to functional and structural modification of collagen elasticity.