ROLE OF NITRIC-OXIDE IN THE REGULATION OF THE MECHANICAL-PROPERTIES OF PERIPHERAL CONDUIT ARTERIES IN HUMANS

Whether nitric oxide (NO) contributes to the regulation of the mechani cal properties of large arteries in humans is not known. We measured t he effect of local administration of the inhibitor of NO synthesis N-G -monomethyl-L-arginine (L-NMMA; 1 and 4 mu mol.L-1.min(-1) for 5 minut es) and acetylcholine (3 and 30 nmol.L-1.min(-1) for 3 minutes) on rad ial artery diameter and wall thickness in 11 healthy volunteers using an echo-tracking system coupled to a measurement of radial blood flow (Doppler) and arterial pressure. At the highest dose, L-NMMA reduced r adial blood flow but surprisingly decreased incremental elastic modulu s (from 1.36+/-0.22 to 1.00+/-0.22 kPa.10(3); P<.05) and increased art erial compliance (from 3.20+/-0.46 to 4.07+/-0.45 m(2).kPa.10(-8), P<. 05), without affecting radial artery internal diameter, wall thickness or midwall stress, thus reflecting a decrease in vascular tone. Acety lcholine decreased incremental elastic modulus (from 1.27+/-0.08 to 0. 88+/-0.07 kPa.10(3); P<.05) and increased arterial diameter, radial bl ood flow, and compliance (from 2.82+/-0.16 to 5.30+/-0.62 m(2).kPa.10( -8); P<.05). These results demonstrate in vivo that NO is involved in the regulation of the mechanical properties of large arteries in human s. However, the effects of L-NMMA, ie, a decrease in arterial wall rig idity and an increase in arterial compliance, which occur in the absen ce of any changes in blood pressure or arterial geometry, suggest that inhibition of NO synthesis is associated in humans with a paradoxical isometric smooth muscle relaxation. This effect could be due to the d evelopment of compensatory vasodilating mechanisms after NO synthesis inhibition.