AGING-ASSOCIATED ENDOTHELIAL DYSFUNCTION IN HUMANS IS REVERSED BY L-ARGININE

Objectives. This study investigated the hypothesis that aging selectiv ely impairs endothelium dependent function, which may reversible by ad ministration of L-arginine, Background: An impaired response to acetyl choline with aging has been demonstrated in humans, However, the mecha nisms underlying this impaired response of the coronary microvasculatu re remain to be determined, Methods. We infused the endothelium-indepe ndent vasodilators papaverine and glyceryl trinitrate (GTN) and the en dothelium-dependent vasodilator acetylcholine (1, 3, 10 and 30 mu g/mi n) into the left coronary artery of 34 patients (27 to 73 years old) w ith atypical chest pain, negative exercise test results, completely no rmal findings on coronary angiography and no coronary risk factors, Co ronary blood Bon was measured with an intracoronary. Doppler catheter, The papaverine and acetylcholine infusions were repeated in 14 patien ts (27 to 73 years old) after an intracoronary. infusion of L-arginine (160 mu mol/min for 20 min). Results. There was a significant negativ e correlation between aging and the peak coronary blood flow response evoked by acetylcholine (r = -0.73, p < 0.0001). However, there was no correlation between aging and the peak coronary blood flow response t o papaverine (r = -0.04, p = 0.82) and GTN (r = -0.24, p = 0.17, The p eak coronary blood flow response evoked by acetylcholine correlated si gnificantly with aging before L-arginine infusion (r = -0.87, p < 0.00 01), but this negative correlation was lost after L-arginine infusion (r = -0.37, p = 0.19). Conclusions. The results suggest that aging sel ectively impairs endothelium-dependent coronary microvascular function and that this impairment can be restored by administration of L-argin ine, a precursor of nitric oxide. (C) 1996 by the American College of Cardiology