ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN FLOW-DEPENDENT DILATION OF HUMAN PERIPHERAL CONDUIT ARTERIES IN-VIVO

Experiments performed in isolated arteries or in animals suggested tha t flow-dependent dilatation of conduit arteries is mediated through th e release of endothelium-derived nitric oxide (NO). The present study was designed to assess whether NO also contributes to flow-dependent d ilatation of conduit arteries in humans. Radial artery internal diamet er was mesured in 8 healthy volunteers (age 22 +/- 1 years), using a t ranscutaneous A-mode echo-tracking system, coupled to a Doppler device for the measurement of radial blood flow. A catheter was inserted in the brachial artery for measurement of arterial pressure and infusion of the L-arginine analogue N(G)-monomethyl L-arginine (L-NAMMA (8 mumo l/min for 7 min, infusion rate 0,8 ml/min). Flow-dependent dilatation was evaluated before and after L-NMMA as the response of the radial ar tery to an acute increase in flow (reactive hyperemia after a 3 min di stal cuff occlusion). Release of the occlusion induced a significant i ncrease in radial blood flow (from 27 +/- 4 to 82 +/- 13 ml/min; p < 0 .01) followed by a delayed increase in radial diameter (flow-mediated dilation; from 2.77 +/- 0.13 to 2.85 +/- 0.13 min; p < 0.01), without any change in heart rate or arterial pressure. L-NMMA induced a signif icant decrease in basal forearm blood flow (from 27 +/- 4 to 14 +/- 2 2 ml/min; p < 0.05), without affecting basal radial artery diameter, h eart rate or arterial pressure. In the pressence of L-NMMA< the peak f low response during hyperemia was not affected (77 +/- 10 ml/min), but the duration of the hyperemic response was significantly reduced, and the flow-dependent dilation of the radial artery was abolished and co nverted to a vasoconstriction (from 2.72 +/- 0.13 to 2.64 +/- 0.13 mm; p < 0.01). Thus, the present investigation demonstrates that NO signi ficantly contributes to reactive hyperemia of the forearm and is essen tial for flow-mediated dilation of human radial arteries in vivo.