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 x kg(-1) by intravenous bolus followed by 3 mg x kg(-1) x h(-1)), norepinephrine (50 ng x kg(-1) x min(-1)), and dobutamine (2.5 to 10 microg x kg(-1) x 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 x 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 x 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.