Nitroglycerin decreases medial smooth muscle cell proliferation after arterial balloon injury.

Abstract

Nitroglycerin and its effector molecules nitric oxide and cyclic guanosine monophosphate decrease smooth muscle cell proliferation in vitro. We examined the in vivo effect of nitroglycerin on intimal hyperplasia. We treated rats after carotid artery balloon injury with nitroglycerin delivered paraarterially with a miniosmotic pump for 1 week. High nitroglycerin serum levels were achieved, and the level of cyclic guanosine monophosphate in the carotid artery wall was significantly increased (1.48 +/- 0.37 vs 0.86 +/- 0.39 pmol/mg protein; p < 0.05) in the nitroglycerin-treated group. Cellular proliferation in the arterial wall was assessed by incorporation of 5-bromo-2'-deoxyuridine 6 days after the injury and was lower in the nitroglycerin-treated group (15.2 +/- 3.4 vs 36.3 +/- 5.5 positive cells/section; p < 0.005). This was due to a decrease in the number of proliferating cells in the media (6.3 +/- 1.2 vs 21.8 +/- 4.5; p < 0.005), whereas in the budding neointima, the difference in the number of proliferating cells was not significant. Neointimal lesions 21 days after the injury did not differ in cross-sectional intimal area, in intimal/medial area ratio, and in cell density. Nitroglycerin decreased medial cellular proliferation after balloon injury and had no significant effect on intimal proliferation. The size of the neointimal lesion was not affected by nitroglycerin therapy.