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 proliferation were examined 24 h and 14 days after balloon injury by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA and expression of proliferating cell nuclear antigen, respectively. Aminoguanidine decreased the luminal area 14 days after balloon injury (0.19+/-0.04 mm2 vs. 0.35+/-0.02 mmr2; P < 0.005), and this effect was attributable to reduction of the total vessel area, i.e., constrictive vascular remodeling (0.42+/-0.03 mm2 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 endothelium-dependent vasorelaxation. We conclude, that in the rat model of balloon injury, aminoguanidine induces luminal loss by constrictive vascular remodeling in association with reduced early VSMC death and increased proliferation.
Department of Cardiology P, Gentofte University Hospital, Hellerup, Denmark. prh@dadlnet.dk
P R
PR
Hansen
A M
AM
Holm
C B
CB
Andersen
S
S
Haunsø
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D020212:Carotid Artery Injuries; D002452:Cell Count / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; C004479:pimagedine