alexa Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature: diminished activity in hypertensive and hypercholesterolemic patients.
Diabetes & Endocrinology

Diabetes & Endocrinology

Journal of Diabetes & Metabolism

Author(s): Paniagua OA, Bryant MB, Panza JA

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Abstract 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 microm) isolated from gluteal fat biopsies were cannulated and perfused in chambers. Shear stress was induced by increasing the flow rate from 1 to 50 microL/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 microL/min to 53+/-14\% at 50 microL/min (P<0.0001), which was abolished by endothelial removal. The NO synthase inhibitor Nomega-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.
This article was published in Circulation and referenced in Journal of Diabetes & Metabolism

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