Myocardin is known as a critical regulator of the vascular smooth muscle cell (SMC) phenotype. By forming a complex with serum response factor (SRF) it binds to the CArG-box motif and triggers the expression of genes supporting the contractile phenotype of these cells. Although its importance for the embryonic differentiation of SMC has been delineated, mechanisms which control its activity during remodelling processes in the adult vasculature are still poorly understood. In this context, we observed that experimentally induced hypertension in mice or increase in circumferential wall tension (CWT) by exposing isolated, murine arteries to a supraphysiological transmural pressure, induces a significant decrease in the abundance of myocardin in SMC. This is accompanied by an increase in proliferation and down-regulation of marker molecules for the contractile phenotype such as calponin. Interestingly, the loss of myocardin is not mediated by the miRNA cluster miR143/145 which is thought to control myocardin expression. To study the mechanism underlying the decline in myocardin, the increase in CWT was mimicked by exposing cultured SMC to cyclic stretch. Stretching reveals a rapid translocation of myocardin from the nucleus to the cytosol which can likewise be mediated by inhibiting its phosphorylation. On the functional level, stretch induced loss of myocardin stimulates the proliferation of cultured SMC and limits their contractile capacity. In conclusion, these observations suggest a hitherto unknown mechanism by which an increase in CWT controls the activity of myocardin. This may contribute to the orchestration of the SMC phenotype during stretch-dependent vascular remodelling processes.