Effects of Inhibition of Basal Nitric Oxide Synthesis on Carotid-Femoral Pulse Wave Velocity and Augmentation Index in Humans

Abstract

Aortic stiffness, as measured by carotid-femoral pulse wave velocity (PWV), is a powerful, independent predictor of vascular risk. PWV in muscular arteries is influenced by basal nitric oxide (NO) release. It is not known whether NO also influences carotid-femoral PWV. We examined the effects of an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), on carotid-femoral PWV and aortic augmentation index (AIx, an indirect measure of arterial stiffness). To control for effects of L-NMMA on distending pressure, we used doses of norepinephrine and dobutamine that caused similar changes in mean arterial blood pressure (MAP). Healthy men (32 to 48 years old, n=8) were studied on 4 occasions and received, in random order, vehicle, L-NMMA (3 mg · kg-1 by intravenous bolus followed by 3 mg · kg -1 · h-1), norepinephrine (50 ng · kg -1 · min-1), and dobutamine (2.5 to 10 μg · kg-1 · min-1), each for 30 minutes. PWV and AIx were measured by carotid-femoral PWV and radial tonometry, respectively. L-NMMA and norepinephrine increased MAP by 7.8±1.7 and 9.7±2.1 mm Hg, respectively (each P<0.05 vs vehicle) and increased PWV by 0.7±0.2 and 1.0±0.3 m · s-1 (each P<0.01 vs vehicle). Dobutamine, at doses that produced a similar increase in MAP (9.6±2.9 mm Hg), increased PWV by 0.8±0.2 m · s -1 (P<0.01 vs vehicle). Changes in PWV caused by the 3 pressor agents were closely correlated with changes in MAP (R>0.99, P<0.0001). L-NMMA and norepinephrine increased AIx, but dobutamine decreased AIx (P<0. 01 vs norepinephrine and L-NMMA). Effects of inhibition of basal NO release on carotid-femoral PWV can be explained by the change in MAP that this causes rather than any specific effect of NO inhibition within the aorta.