[Long-term effects of growth-activating agents on smooth muscle contraction and endothelial function in...

In the endothelium-denuded arteries cultured in the presence of FBS, morphological (i.e. smooth muscle disorientation and increase in collagen fiber) and phenotypic changes in smooth muscle were observed. Correlated with these changes, contractile force induced by high concentration of KCl and norepinephrine was significantly decreased. In addition, Ca-induced contraction in the permeabilized muscle was also significantly reduced. The reduced contractility in the FBS-treated arteries was partially recovered by the treatment with L-NMMA. In the endothelium-intact arteries cultured in the presence of FBS or PDGF, substance P and ionomycin-mediated, endothelium-dependent relaxation (EDR) was significantly decreased compared to the arteries cultured in serum-free condition. In addition, amounts of NO production and total recoverable eNOS mRNA was reduced in the FBS and PDGF-treated arteries. In these arteries, however, cGMP-dependent relaxation in smooth muscle was not impaired. These results suggest that long-term treatment of vascular tissue with growth-activating agents causes morphological or phenotypic changes nad up-regulation of NO production in smooth muscle, resulting in a reduced contractility. Furthermore, longterm treatment with these agents impairs NO-mediated EDR by decreasing eNOS mRNA and NO production.