Retinol influences contractile function and exerts an anti-proliferative effect on vascular smooth muscle cells...

Rat aortic rings maintained in organ culture for as little as 24 h show 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. Rat aortic ring segments cultured in retinol supplemented (10(-6) M) medium showed significantly increased active tension development in response to 80 mM K+ depolarization compared with 7-day cultured control rings. The improvement of contractile performance of the cultured aorta segments in retinol-supplemented media was lost when rings were denuded of endothelium prior to culture, suggesting the endothelial cell layer 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 aortic endothelial cells (BAEC). It was further observed that media conditioned with BAEC treated with 10(-6) M retinol expressed SMC growth inhibitory properties compared with media conditioned by untreated BAEC cells or unconditioned media. Examination of cultured rat aortic ring segments by electron microscopy and BAEC cells with phase contrast microscopy revealed that retinol had obvious effects on endothelial cell morphology and ultrastructure. These results indicate that retinol exerts its effects primarily on the endothelium, which in turn secretes stable factors that directly affect SMC proliferation and contractility.