© 1999 American Heart Association, Inc.
Vascular Biology |
Protection by Shear Stress From Collar-Induced Intimal Thickening
Role of Nitric Oxide
From Laboratorio di Farmacologia (G.M., S.P.), Istituto Superiore di Sanità, Rome; Istituto di Anestesia e Rianimazione (A.V.), Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome; Cattedra di Cardioangiologia Medica (A.U.F.), Centro Fisiologia Clinica e Ipertensione, University of Milan; CNR and IRCSS Ospedale Maggiore (A.U.F.), Milan, Italy.
Correspondence to Giuseppe Marano, MD, Laboratorio di Farmacologia, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. E-mail gmarano{at}iss.it
Abstract—Nitric oxide (NO) has
potent relaxant and antiproliferative effects on vascular smooth muscle
cells, which may represent an important antiatherosclerotic
mechanism. Since one of the major stimuli for NO release is
flow-related shear stress, we have investigated (1) the effect of
increased shear stress on neointimal formation induced in
the rabbit carotid artery by enclosing the vessel in a nonconstrictive
silicone soft collar and (2) the role of NO in the antiproliferative
effect of increased shear stress. Forty-three New Zealand White rabbits
were used. High shear stress in the left common carotid artery (CCA)
was induced by ligature of the contralateral right internal carotid
artery; intimal thickening was produced by the positioning a
nonconstrictive silicone soft collar around the left CCA. To evaluate
the role of NO,
NG-nitro-L-arginine methyl ester
(L-NAME) was orally administered at a 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
euthanized, and histological analyses were
performed on both CCAs of each animal. The presence of the collar was
associated with a marked degree of intimal hyperplasia (intimal/medial
area ratio 29±3.0% in collared arteries compared with 3±0.7% in
sham control [noncollared] arteries, P<0.001). The
increase in blood flow almost completely inhibited
neointimal formation and induced an increase in
arterial diameter of 
30%. The effects of increased
blood flow were reversed by the administration of L-NAME. In
conclusion, we demonstrate that in collar-induced intimal thickening, a
chronic increase in shear stress (1) almost completely inhibits intimal
thickening, and (2) this protective effect is mediated by NO
production.
Key Words: shear stress • intimal hyperplasia • collar model • nitric oxide • flow-dependent vasodilation • rabbits
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