ROLE OF BASAL AND STIMULATED RELEASE OF NITRIC-OXIDE IN THE REGULATION OF RADIAL ARTERY CALIBER IN HUMANS

Although it is well established that nitric oxide contributes to the r egulation of resistance arterial tone in humans, its role at the level of large arteries is less clear. Therefore, we assessed in healthy vo lunteers the effects of local administration of the inhibitor of nitri c oxide synthesis N-G-monomethyl-L-arginine (L-NMMA) on basal radial a rtery diameter (transcutaneous A-mode echotracking) and radial blood f low (Doppler) as well as on the radial response to acetylcholine and t he nitric oxide donor sodium nitroprusside. A catheter was inserted in to the brachial artery for measurement of arterial pressure and infusi on of L-NMMA (2, 4, and 8 mu mol/min for 5 minutes, n=11), acetylcholi ne (3, 30, 300, and 900 nmol/min for 3 minutes, n=8), and nitroprussid e (2.5, 5, 10, and 20 nmol/min for 3 minutes, n=6). None of the treatm ents affected arterial blood pressure or heart rate. L-NMMA dose-depen dently decreased radial blood flow (from 31+/-6 to 17+/-3 10(-3) L/min after 8 mu mol/min, P<.01) but did not affect radial artery diameter (from 2.93+/-0.11 to 2.90+/-0.14 mm). Acetylcholine dose-dependently i ncreased radial blood flow (154+/-43% after 900 nmol/min) and radial a rtery diameter (16+/-4%), and both effects were markedly reduced after L-NMMA (increase in radial blood flow and radial artery diameter: 22/-20% and 3+/-2%, respectively; both P<.01 versus controls). Nitroprus side also dose-dependently increased radial artery diameter (14+/-4% a fter 20 nmol/min) but only moderately affected radial blood flow (47+/ -21%). L-NMMA markedly increased the effects of nitroprusside on radia l artery diameter (26+/-2%, P<.01 versus controls) but not on radial b lood flow (66+/-21%, P=NS versus controls). These experiments demonstr ate for the first time that large peripheral arteries vasodilate in re sponse to acetylcholine in vivo through the release of endogenous nitr ic oxide. The increased sensitivity to nitrovasodilators after L-NMMA suggests the existence of a basal release of nitric oxide at the level of large peripheral arteries. However, the lack of a decrease in diam eter after L-NMMA might be explained by the presence of compensating v asodilator mechanisms occurring at the level of large arteries after i nhibition of nitric oxide synthesis.