Endothelial modulation of DNA synthesis in isolated arteries of the rat.

The endothelium can modulate the supply of growth factors to the underlying smooth muscle. In vitro experiments suggest that it may also influence the responsiveness of arterial smooth muscle to mitogens. In these experiments, we measured DNA synthesis in segments of carotid and renal arteries that were isolated from Wistar-Kyoto (WKY) rats and exposed to serum. Nuclear incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdUrd), was visualized by immunocytochemistry and the percentage of labeled nuclei (BrdUrd L%) was determined in the tunica media. In both types of artery isolated from 6- and 20-week-old WKY rats, mechanical removal of endothelium increased the BrdUrd L% in the tunica media. In carotid arteries of 20-week-old WKY rats, gentle denudation increased the incorporation of [3H]thymidine but not [14C]leucine. In denuded renal arteries of adult WKY rats, exogenous prostaglandin E2, iloprost, and transforming growth factor-beta (TGF-beta) reduced media labeling, which was not affected by Na nitroprusside. In renal arteries with endothelium, methylene blue and indomethacin did not affect medial DNA synthesis. These findings demonstrate that in arteries of young and adult rats, the endothelium reduces stimulated DNA synthesis. It is unlikely that basal production of nitric oxide or prostaglandins is involved herein. Endothelial inhibition of DNA synthesis but not protein synthesis in arteries indicates that the endothelium may influence the extent of arterial smooth muscle hypertrophy and hyperplasia.