Published online before print September 15, 2003, doi: 10.1161/01.HYP.0000092882.65699.19
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(Hypertension. 2003;42:915.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
Effects of Inhibition of Basal Nitric Oxide Synthesis on Carotid-Femoral Pulse Wave Velocity and Augmentation Index in Humans
From the Department of Clinical Pharmacology, St Thomas’ Hospital (A.D.S., S.C.M., J.M.R., P.J.C.), and the Department of Cardiology, King’s College Hospital (M.T.K.), King’s College, London, UK.
Correspondence to Dr Philip J. Chowienczyk, Department of Clinical Pharmacology, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH UK. E-mail phil.chowienczyk{at}kcl.ac.uk
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.
Key Words: aorta • elasticity • endothelium • nitric oxide • nitric oxide synthase
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