RETINOL INFLUENCES CONTRACTILE FUNCTION AND EXERTS AN ANTIPROLIFERATIVE EFFECT ON VASCULAR SMOOTH-MUSCLE CELLS THROUGH AN ENDOTHELIUM-DEPENDENT MECHANISM

Rat aortic rings maintained in organ culture for as little as 24 h sho w significant loss of contractile responsiveness to different agonists . Smooth muscle cells (SMC) in culture quickly de differentiate into a non-contractile phenotype with a marked capacity for proliferation. R at aortic ring segments cultured in retinol supplemented (10(-6) M) me dium showed significantly increased active tension development in resp onse to 80 mM K+ depolarization compared with 7-day cultured control r ings. The improvement of contractile performance of the cultured aorta segments in retinol-supplemented media was lost when rings were denud ed of endothelium prior to culture, suggesting the endothelial cell la yer as the mediator of this effect. Retinol at concentrations up to 10 (-5) M was found to have no direct effect on proliferation of cells of the A7r5 SMC. However, retinol was found to augment significantly the growth inhibition of A7r5 cells grown in co-culture with bovine aorti c endothelial cells (BAEC). It was further observed that media conditi oned with BAEC treated with 10(-6) M retinol expressed SMC growth inhi bitory properties compared with media conditioned by untreated BAEC ce lls or unconditioned media. Examination of cultured rat aortic ring se gments by electron microscopy and BAEC cells with phase contrast micro scopy revealed that retinol had obvious effects on endothelial cell mo rphology and ultrastructure. These results indicate that retinol exert s its effects primarily on the endothelium, which in turn secretes sta ble factors that directly affect SMC proliferation and contractility.