Laughlin, M. Harold

Aging has been recently associated with increased retrograde and oscillatory shear in peripheral conduit arteries, a hemodynamic environment that favors a proatherogenic endothelial cell phenotype. We evaluated whether nitric oxide (NO) bioavailability in resistance vessels contributes to age-related differences in shear rate patterns in upstream conduit arteries at rest and during rhythmic muscle contraction. Younger (n=11, age 26±2 years) and older (n=11, age 61±2 years) healthy subjects received intra-arterial saline (control) and the NO synthase inhibitor N G -Monomethyl- l -arginine. Brachial artery diameter and velocities were measured via Doppler ultrasound at rest and during a 5-minute bout of rhythmic forearm exercise. At rest, older subjects exhibited greater brachial artery retrograde and oscillatory shear (−13.2±3.0 s −1 and 0.11±.0.02 arbitrary units, respectively) compared with young subjects (−4.8±2.3 s −1 and 0.04±0.02 arbitrary units, respectively; both P <0.05). NO synthase inhibition in the forearm circulation of young, but not of older, subjects increased retrograde and oscillatory shear (both P <0.05), such that differences between young and old at rest were abolished (both P >0.05). From rest to steady-state exercise, older subjects decreased retrograde and oscillatory shear (both P <0.05) to the extent that no exercise-related differences were found between groups (both P >0.05). Inhibition of NO synthase in the forearm circulation did not affect retrograde and oscillatory shear during exercise in either group (all P >0.05). These data demonstrate for the first time that reduced NO bioavailability in the resistance vessels contributes, in part, to age-related discrepancies in resting shear patterns, thus identifying a potential mechanism for increased risk of atherosclerotic disease in conduit arteries.