NITRIC-OXIDE IS RESPONSIBLE FOR FLOW-DEPENDENT DILATATION OF HUMAN PERIPHERAL CONDUIT ARTERIES IN-VIVO

Background Experimental evidence suggests that flow-dependent dilatati on of conduit arteries is mediated by nitric oxide (NO) and/or prostac yclin. The present study was designed to assess whether NO or prostacy clin also contributes to flow-dependent dilatation of conduit arteries in humans. Methods and Results Radial artery internal diameter (ID) w as measured continuously in 16 healthy volunteers (age, 24+/-1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a cat heter was inserted into the brachial artery for measurement of arteria l pressure and infusion of the NO synthase inhibitor N-G-monomethyl-L- arginine (L-NMMA; 8 mu mol/min for 7 minutes; infusion rate, 0.8 mL/mi n). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion induced a marked increas e in radial blood flow (from 24+/-3 to 73+/-11 mL/min; P<.01) followed by a delayed increase in radial diameter (how-mediated dilatation; fr om 2.67+/-0.10 to 2.77+/-0.12 mm; P<.01) without any change in heart r ate or arterial pressure. L-NMMA decreased basal forearm blood flow (f rom 24+/-3 to 13+/-3 mL/min; P<.05) without affecting basal radial art ery diameter, heart rate, or arterial pressure, whereas aspirin (1 g P O) was without any hemodynamic effect. In the presence of L-NMMA, the peak flow response during hyperemia was not affected (76+/-12 mL/min), but the duration of the hyperemic response was markedly reduced, and the flow-dependent dilatation of the radial artery was abolished and c onverted to a vasoconstriction (from 2.62+/-0.11 to 2.55+/-0.11 mm; P< .01). In contrast, aspirin did not affect the hyperemic response nor t he flow-dependent dilatation of the radial artery. Conclusions The pre sent investigation demonstrates that NO, but not prostacyclin, is esse ntial for flow-mediated dilatation of large human arteries. Hence, thi s response can be used as a test for the L-arginine/NO pathway in clin ical studies.