(Circulation. 2001;103:1752.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Role of Endothelial Nitric Oxide in Shear Stress–Induced Vasodilation of Human Microvasculature
Diminished Activity in Hypertensive and Hypercholesterolemic Patients
From the Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Correspondence to Dr Julio A. Panza, National Institutes of Health, 10 Center Dr, MSC 1650, Bldg 10, Room 7B-15, Bethesda, MD 20892-1650. E-mail panzaj{at}nih.gov
Background—It has been proposed that flow-mediated shear stress regulates vascular tone; however, whether this operates in the human microcirculation is unknown. This study was designed to investigate the effect of shear stress on human microvascular tone, to assess the contribution of nitric oxide (NO), and to determine whether this mechanism is defective in hypertension and in hypercholesterolemia.
Methods and
Results—In 9 normal controls (NC), 11
hypertensive patients (HT), and 12 hypercholesterolemic patients
(HChol), arteries (internal diameter 201±26 µm) isolated from
gluteal fat biopsies were cannulated and perfused in chambers. Shear
stress was induced by increasing the flow rate from 1 to 50 µL/min
after preconstriction with norepinephrine (NE). Arterial internal
diameter was expressed as percent of NE-induced constriction. In NC,
shear stress induced flow-dependent vasodilation from 23±9% at 1
µL/min to 53±14% at 50 µL/min
(P<0.0001), which was
abolished by endothelial removal. The NO synthase inhibitor
N
-nitro-L-arginine
(L-NNA) significantly blunted this response (mean vasodilation
decreased from 27±6% to 6±9%;
P=0.04). HT had significant
impairment of flow-mediated dilation (mean vasodilation 5±6%;
P=0.01 versus NC), which was
not affected by L-NNA. HChol had preserved flow-mediated vasodilation
(mean vasodilation 24±7%;
P=0.56 versus NC), but this was
not significantly modified by L-NNA.
Conclusions—In the human microvasculature, shear stress induces endothelium-dependent, NO-mediated vasodilation. This phenomenon is blunted in HT patients because of reduced activity of NO. In contrast, the HChol microvasculature has preserved shear stress-induced dilation despite diminished NO activity.
Key Words: microcirculation • endothelium • nitric oxide • hypertension • hypercholesterolemia
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