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, N ^G -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 −1 (each P −1 ( P 0.99, P 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.