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 regulation of resistance arterial tone in humans, its role at the level of large arteries is less clear. Therefore, we assessed in healthy volunteers the effects of local administration of the inhibitor of nitric oxide synthesis N-G-monomethyl-L-arginine (L-NMMA) on basal radial artery diameter (transcutaneous A-mode echotracking) and radial blood flow (Doppler) as well as on the radial response to acetylcholine and the nitric oxide donor sodium nitroprusside. A catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of L-NMMA (2, 4, and 8 mu mol/min for 5 minutes, n=11), acetylcholine (3, 30, 300, and 900 nmol/min for 3 minutes, n=8), and nitroprusside (2.5, 5, 10, and 20 nmol/min for 3 minutes, n=6). None of the treatments affected arterial blood pressure or heart rate. L-NMMA dose-dependently 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 increased radial blood flow (154+/-43% after 900 nmol/min) and radial artery 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). Nitroprusside also dose-dependently increased radial artery diameter (14+/-4% after 20 nmol/min) but only moderately affected radial blood flow (47+/-21%). L-NMMA markedly increased the effects of nitroprusside on radial artery diameter (26+/-2%, P<.01 versus controls) but not on radial blood flow (66+/-21%, P=NS versus controls). These experiments demonstrate for the first time that large peripheral arteries vasodilate in response to acetylcholine in vivo through the release of endogenous nitric 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 diameter after L-NMMA might be explained by the presence of compensating vasodilator mechanisms occurring at the level of large arteries after inhibition of nitric oxide synthesis.