Protection by shear stress from collar-induced intimal thickening - Role of nitric oxide

Nitric oxide (NO) has potent relaxant and antiproliferative effects on vasc ular smooth muscle cells, which may represent an important antiatherosclero tic mechanism. Since one of the major stimuli for NO release is flow-relate d shear stress, we have investigated (1) the effect of increased shear stre ss on neointimal formation induced in the rabbit carotid artery by enclosin g the vessel in a nonconstrictive silicone soft collar and (2) the role of NO in the antiproliferative effect of increased shear stress. Forty-three N ew Zealand White rabbits were used. High shear stress in the left common ca rotid artery (CCA) was induced by ligature of the contralateral right inter nal carotid artery; intimal thickening was produced by the positioning a no nconstrictive silicone soft collar around the left CCA. To evaluate the rol e of NO, N-G-nitro-L-arginine methyl eater (L-NAME) was orally administered ate subpressor dose. In all rabbits, arterial blood pressure, heart rate, arterial diameters, and blood flow velocities of both CCAs were determined at days 0, 3, 7, and 14. At the end of the study, all rabbits were euthaniz ed, and histological analyses were performed on both CCAs of each animal. T he presence of the collar was associated with a marked degree of intimal hy perplasia (intimal/medial area ratio 29 +/- 3.0% in collared arteries compa red with 3 +/- 0.7% in sham control [noncollared] arteries, P < 0.001). The increase in blood flow almost completely inhibited neointimal formation an d induced an increase in arterial diameter of approximate to 30%. The effec ts of increased blood flow were reversed by the administration of L-NAME. I n conclusion, we demonstrate that in collar-induced intimal thickening, a c hronic increase in shear stress (1) almost completely inhibits intimal thic kening, and (2) this protective effect is mediated by NO production.