Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature - Diminished activity in hypertensive and hypercholesterolemic patients

Background-It has been proposed that flow-mediated shear stress regulates v ascular tone; however, whether this operates in the human microcirculation is unknown. This study was designed to investigate the effect of shear stre ss 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), 1 1 hypertensive patients (H T), and 12 hypercholesterolemic patients (HChol), arteries (internal diamet er 201 +/- 26 mum) isolated from gluteal fat biopsies were cannulated and p erfused in chambers. Shear stress was induced by increasing the flow rate f rom 1 to 50 muL/min after preconstriction with norepinephrine (NE). Arteria l internal diameter was expressed as percent of NE-induced constriction. In NC, shear stress induced flow-dependent vasodilation from 23 +/-9% at 1 mu L/min to 53 +/- 14% at 50 muL/min (P<0.0001), which was abolished by endoth elial removal, The NO synthase inhibitor Nw-nitro-L-arginine (L-NNA) signif icantly blunted this response (mean vasodilation decreased from 27<plus/min us>6% to 6 +/-9%; P=0.04). HT had significant impairment of flow-mediated d ilation (mean vasodilation 5 +/-6%; P=0.01 versus NC), which was not affect ed by L-NNA. HChol had preserved now-mediated vasodilation (mean vasodilati on 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 pati ents because of reduced activity of NO. Tn contrast, the HChol microvascula ture has preserved shear stress-induced dilation despite diminished NO acti vity.