Aminoguanidine induces constrictive vascular remodeling and inhibits smooth muscle cell death after balloon injury

We examined the effects of aminoguanidine, an inhibitor of inducible nitric oxide synthase, in the rat model of balloon injury, Arteries were assessed by histomorphometry, and vascular smooth muscle cell death and proliferati on were examined 24 h and 14 days after balloon injury by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) of fra gmented DNA and expression of proliferating cell nuclear antigen, respectiv ely. Aminoguanidine decreased the luminal area 14 days after balloon injury (0.19 +/- 0.04 mm(2) vs. 0.35 +/- 0.02 mm(2); P < 0.005), and this effect was attributable to reduction of the total vessel area, i.e., constrictive vascular remodeling (0.42 +/- 0.03 mm(2) vs. 0.55 +/- 0.03 mm2; P < 0.005). At 24 h after injury, the percentage of TUNEL-positive cells in the medial layer was reduced by aminoguanidine (2.0 +/- 1.0% vs. 17.3 +/- 5.4%; P < 0 .05), and the percentage of proliferating cells was increased (18.4 +/- 5.5 % vs. 4.9 +/- 2.2%; P < 0.05). Aminoguanidine did not influence the density of VSMC nuclei in the injured artery wall, systemic blood pressure or endo thelium-dependent vasorelaxation. We conclude, that in the rat model of bal loon injury, aminoguanidine induces luminal loss by constrictive vascular r emodeling in association with reduced early VSMC death and increased prolif eration. (C) 1999 Elsevier Science B.V. All rights reserved.