CHRONIC INHALATION OF NITRIC-OXIDE INHIBITS NEOINTIMAL FORMATION AFTER BALLOON-INDUCED ARTERIAL INJURY

Systemic and local intravascular NO administration inhibits neointimal formation after vascular injury in animal models. NO appears to atten uate smooth muscle proliferation both directly and indirectly by preve nting the release of growth factors. Inhalation of low concentrations of NO dilates pulmonary vascular smooth muscle but does not cause syst emic vasodilatation. Recently, NO inhalation was found to inhibit plat elet function in vivo. We studied the effects of NO inhalation on neoi ntimal formation after balloon-induced injury of the adult rat carotid artery. Beginning 60 minutes before carotid injury, rats breathed eit her air with 0 or 80 ppm NO for 14 days. Rats were killed, carotid art eries were fixed and paraffin-embedded, and neointimal formation was m easured by analyzing the ratio of intimal to medial areas (I/M ratio) in carotid artery cross sections. Intimal hyperplasia was evident in b oth groups of animals, but I/M ratios were 43% less in animals breathi ng 80 ppm NO for 2 weeks than in animals breathing air alone (0.78+/-0 .12 and 1.37+/-0.11 [mean+/-SE], respectively; P<.02). Similarly, 1 we ek after carotid injury, neointimal formation was less in rats breathi ng 80 ppm NO than in rats breathing air alone (I/M ratio, 0.39+/-0.11 versus 0.76+/-0.06; P<.02). Breathing 20 ppm NO for 2 weeks or 80 ppm NO for 1 week followed by air alone for 1 week did not attenuate neoin timal formation measured al 14 days. In anesthetized rats breathing 80 ppm NO or air alone for 1 hour, neither systemic blood pressure nor b leeding time differed. These observations demonstrate that inhaling 80 ppm NO inhibits neointimal formation after balloon-induced carotid ar tery injury in rats. NO inhalation may represent a safe and novel meth od of preventing restenosis after percutaneous angioplasty.