[Influence of vasoactive peptides on homocysteine-induced proliferation of cultured rabbit vascular smooth muscle cell].

OBJECTIVE

To study the effects of vasoactive peptides [adrenomedullin (Adm), C-type natriuretic peptide (CNP), calcitonin gene related peptide (CGRP), somatostatin(SST) and parathyroid hormone-related protein] on homocysteine (Hcy)-induced proliferation of cultured rabbit vascular smooth muscle cell (VSMC).

METHODS

Techniques of cell culture, 3H-thymidine incorporation, nuclei, membrane and cytosol fractions were isolated by differential centrifugation and PKC activity was measured.

RESULTS

Hcy significantly stimulated DNA synthesis of VSMC. Adm, CNP, CGRP, SST, and PTHrP had no effect on basal 3H-TdR incorporation, but they could inhibit Hcy-induced 3H-TdR incorporation in dose-dependent manner. PKC inhibitor (H7 and Stauroporine) could inhibit VSMC proliferation induced by Hcy with reduction of 3H-TdR incorporation by 50% (P < 0.01) and 56% (P < 0.01), respectively. PKC was found to be distributed equally in nuclear fraction and membrane particulate, and higher in cytosol fraction in untreated VSMC. Treatment of VSMC with 10(-4) mol/L Hcy resulted in a significant increase in membrane-associated PKC combined with a loss of enzyme activity in the cytosol and nuclear fractions. Adm, CNP, CGRP and PTHrP altered the distribution of PKC activity induced by Hcy.

CONCLUSION

Adm, CNP, CGRP and PTHrP inhibited VSMC proliferation possibly through PKC pathway.