Failure of cdc2 promoter activation and G2/M transition by ANG II and AVP in vascular smooth muscle cells

The physiological role of the vasoconstrictive hormones arginine vasopressin (AVP) and angiotensin Ii (ANG II) in the development of vascular hyperplasia is still unclear. We examined the effects of these hormones on cell cycle regulation of cultured rat vascular smooth muscle cells (VSMC). AVP and ANG II were able to induce G(1)/S transition and DNA synthesis in serum-starved quiescent VSMC but failed to promote further progression into G(2)/M phases. AVP and ANG II enhanced the expression and activity of cdk2, cyclin E, and proliferating cell nuclear antigen but did not induce expression of cdc2/cyclin B complex, a critical regulator of G(2)/M transition. The failure of cdc2 mRNn induction was found to be caused by a defect in cdc2 promoter activation. Binding of free E2F-1 to the cdc2 promoter did not occur in hormone-treated VSMC, which may account for the defective induction of cdc2. The absence of cdc2 promoter activation and G(2)/M transition may be important for the prevention of hyperplasia under physiological conditions but underlies the hypertrophy of VSMC.