INTRALUMINAL PRESSURE IS ESSENTIAL FOR THE MAINTENANCE OF SMOOTH-MUSCLE CALDESMON AND FILAMIN CONTENT IN AORTIC ORGAN-CULTURE

Different forms of mechanical stimulation are among the physiological factors constantly acting on the vessel wall. We previously demonstrat ed that subjecting vascular smooth muscle cells (VSMCs) in culture to cyclic stretch increased the expression of high-molecular-weight calde smon, a marker protein of a differentiated, contractile, VSMC phenotyp e. In the present work the effects of mechanical factors, in the form of circumferential stress and shear stress, on the characteristics of SM contractile phenotype were studied in an organ culture of rabbit ao rta. Application of an intralumininal pressure of 80 mm Hg to aortic s egments cultured in Dulbecco's modified Eagle's medium containing 20% fetal calf serum for 3 days prevented the decrease in high-molecular-w eight caldesmon content (70+/-4% of initial level in nonpressurized ve ssel, 116+/-17% at 80 mm Hg) and filamin content (80+/-5% in nonpressu rized vessel, 100+/-2% at 80 mm Hg). SM myosin and low-molecular-weigh t caldesmon contents showed no dependence on vessel pressurization. Ne ither endothelial denudation nor alteration of intraluminal flow rates affected marker protein content in 3-day vessel culture, thus excludi ng the possibility of any shear or endothelial effects. Maintenance of high high-molecular-weight caldesmon and filamin levels in the organ cultures of pressurized and stretched vessels demonstrates the positiv e role of mechanical factors in the control of the VSMC differentiated phenotype.