EFFECT OF RETINOIC ACID ON CONTRACTILE COMPETENCE OF VASCULAR SMOOTH-MUSCLE

Rat aortic rings cultured for 24 h in protein-free medium showed a sig nificant reduction in the contractile response to potassium (-60%) and to phorbol 12,13-dibutyrate (-65%). The addition of plasma to the med ium attenuated the loss in responsiveness, and the supplementation of the plasma-containing medium with all trans-retinoic acid (RA) returne d the response to potassium (85%) and phorbol ester (135%) to near nor mal or supramaximal compared with fresh tissue. Furthermore, the combi ned additions of plasma and RA resulted in significant preservation of the contractile response (75%) for at least 3 days in organ culture. Removal of the endothelium before organ culture eliminated the enhance ment of contraction by plasma and RA. However, the removal of the endo thelium from tissues that had been cultured with an intact endothelium or the blockade of nitric oxide synthesis in these tissues before con tractile measurements had no effect on the contractile response. Final ly, the incubation of tissues with phorbol ester to downregulate prote in kinase C resulted in a marked attenuation (-75%) of the contractile response compared with control tissues in culture. The results sugges t that circulating factors may be necessary for the maintenance of con tractile function of aortic smooth muscle. Based on the opposing actio ns of RA and phorbol ester, the long-term regulation of contractile fu nction may involve protein kinase C activity.