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Nitroglycerin decreases medial smooth muscle cell proliferation after arterial balloon injury
Y G Wolf1, L M Rasmussen, Y Sherman
1Department of Surgery, School of Medicine, University of California San Diego.
Purpose:
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.
Methods:
We treated rats after carotid artery balloon injury with nitroglycerin delivered paraarterially with a miniosmotic pump for 1 week.
Results:
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.
Conclusion:
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.