EFFECTS OF CANDIDATE AUTOCRINE AND PARACRINE MEDIATORS ON GROWTH-RESPONSES IN ISOLATED RAT ARTERIES

We evaluated the effects of mediators that can be produced by smooth m uscle and endothelial cells on growth responses in isolated arteries. Segments of carotid and renal arteries, denuded of endothelium, were i solated from adult rats and studied during tissue Culture in the prese nce of indomethacin. Three days of culture in the presence of serum st imulated DNA synthesis in the media. During long-term culture new laye rs of cells developed at the borders of the arterial segments. Medial DNA synthesis depended less on serum than extramedial cell proliferati on. During moderate stimulation, basic fibroblast growth factor and en dothelin-1 enhanced and interleukin-1 and transforming growth factor-b eta reduced medial DNA synthesis, whereas insulin-like growth factor-1 , platelet-derived growth factor AA, platelet-derived growth factor BB , and angiotensin II were without effect. Of these factors, only endot helin-1 stimulated extramedial cell proliferation. In addition, serum- stimulated but not basic fibroblast growth factor-stimulated medial DN A synthesis was less marked in arteries that had not been denuded of e ndothelium than in de-endothelialized arteries. Differences between pr eparations with and without endothelium persisted in the absence of L- arginine and in the presence of an inhibitor of nitric oxide synthase. These observations confirmed that DNA synthesis in the arterial media and extramedial cell proliferation are influenced by different factor s. They further indicated that endothelial modulation of medial DNA sy nthesis does not seem to involve endothelium-derived prostaglandins, n itric oxide, or interleukin-1 and that it can be blunted by basic fibr oblast growth factor.