The antiproliferative effects of calcitonin gene-related peptide in different passages of cultured vascular smooth muscle cells

Previously our laboratory showed that calcitonin gene-related peptide (CGRP) is released from perivascular nerves exposed to endotoxin or inflammatory mediators bradykinin and prostaglandins CGRP contributes significantly to the vasodilation of inflammation and septic shock. Another potential action of CGRP is inhibition of vascular smooth muscle cell (VSMC) growth, which could serve to counterbalance the stimulatory effects of IL-1 and TNF on VSMC proliferation. VSMCs from rabbit and rat aorta (in the second and fifth passages) were plated at 100 000 cells/well in 24-well trays in 10% fetal bovine serum (FBS) for 24 h, incubated for an additional 24 h without FBS, and then exposed to 2.5% FBS for 24 h in the presence or absence of CGRP. H-3-thymidine incorporation was used to measure DNA synthesis and proliferation. CGRP caused significant inhibition of H-3-thymidine incorporation, which correlated with elevations of cAMP in both rat and rabbit aortic VSMCs. Interestingly, the responses of both the elevation of cAMP and the inhibition of DNA synthesis became larger in VSMCs with an increasing number of passages. The data suggest that the CGRP, released during vascular inflammation, may serve to inhibit the proliferation of VSMCs, thus limiting the growth of atheromatous lesions.