(Circulation. 1995;91:1314-1319.)
© 1995 American Heart Association, Inc.
Articles |
Nitric Oxide Is Responsible for Flow-Dependent Dilatation of Human Peripheral Conduit Arteries In Vivo
From the Department of Pharmacology, VACOMED, IFRMP, Rouen University Medical School and Rouen Hospital (France) (R.J., V.R., E.H.B., C.T.) and the Department of Clinical Pharmacology, Basel University Hospital (Switzerland) (W.E.H., L.L., T.F.L.).
Correspondence to T.F. Lüscher, MD, Cardiology, University Hospital, CH 4031, Bern, Switzerland.
Background Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans.
Methods and Results Radial artery internal diameter (ID) was 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 catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 8 µmol/min for 7 minutes; infusion rate, 0.8 mL/min). 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 increase in radial blood flow (from 24±3 to 73±11 mL/min; P<.01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.67±0.10 to 2.77±0.12 mm; P<.01) without any change in heart rate or arterial pressure. L-NMMA decreased basal forearm blood flow (from 24±3 to 13±3 mL/min; P<.05) without affecting basal radial artery diameter, heart rate, or arterial pressure, whereas aspirin (1 g PO) 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 converted 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 the flow-dependent dilatation of the radial artery.
Conclusions The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the L-arginine/NO pathway in clinical studies.
Key Words: blood flow • endothelium-derived factors • L-NMMA • arteries • dilation
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