Nitric oxide (NO)-based
therapies effectively inhibit neointimal
hyperplasia in animal models of arterial injury and bypass grafting, but are not available clinically. We created a simple, effective, locally applied NO-eluting
therapy to prevent restenosis after vascular procedures. We investigated the efficacy of perivascular delivery of two distinctly different
diazeniumdiolate NO donors, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (
PROLI/NO) (short half-life) and
diazeniumdiolated poly(acrylonitrile) (PAN/NO) (long half-life), in
powder or gel form (30%
poloxamer 407), at inhibiting neointimal
hyperplasia using the rat
carotid artery injury model. Two weeks postinjury, all of the NO-eluting
therapies successfully reduced neointimal
hyperplasia. However, most dramatically,
PROLI/NO powder reduced intimal area by 91.2% (p<0.05) versus injury alone.
PROLI/NO powder was noted to reduce the medial area (40.2% vs injury alone, p<0.05), whereas other groups showed no such effect. Three days postinjury, each NO treatment group significantly reduced cellular proliferation. However, inflammatory markers revealed a distinct pattern: PAN/NO groups displayed increased leukocyte infiltration (p<0.05), whereas
PROLI/NO groups displayed less macrophage infiltration (p<0.05). In conclusion, perivascular delivery of
diazeniumdiolate NO donors in
powder or gel form effectively inhibits neointimal
hyperplasia. Application of short-acting
PROLI/NO powder most effectively inhibited neointimal
hyperplasia and
inflammation and may represent a simple, clinically applicable NO-eluting
therapy to prevent neointimal
hyperplasia and restenosis after open vascular interventions.