title: Role of nitric oxide in the regulation of the mechanical properties of peripheral conduit arteries in humans.
abstract: Whether nitric oxide (NO) contributes to the regulation of the mechanical properties of large arteries in humans is not known. We measured the effect of local administration of the inhibitor of NO synthesis N(G)-monomethyl-L-arginine (L-NMMA; 1 and 4 micromol x L[-1] x min[-1] for 5 minutes) and acetylcholine (3 and 30 nmol x L[-1] x min[-1] for 3 minutes) on radial 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 radial blood flow but surprisingly decreased incremental elastic modulus (from 1.36+/-0.22 to 1.00+/-0.22 kPa x 10[3]; P<.05) and increased arterial compliance (from 3.20+/-0.46 to 4.07+/-0.45 m2 x kPa x 10(-8), P<.05), without affecting radial artery internal diameter, wall thickness or midwall stress, thus reflecting a decrease in vascular tone. Acetylcholine decreased incremental elastic modulus (from 1.27+/-0.08 to 0.88+/-0.07 kPa x 10[3]; P<.05) and increased arterial diameter, radial blood flow, and compliance (from 2.82+/-0.16 to 5.30+/-0.62m2 x kPa x 10[-8]; P<.05). These results demonstrate in vivo that NO is involved in the regulation of the mechanical properties of large arteries in humans. However, the effects of L-NMMA, ie, a decrease in arterial wall rigidity and an increase in arterial compliance, which occur in the absence 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 development of compensatory vasodilating mechanisms after NO synthesis inhibition.
authors.affiliation: Department of Pharmacology, Vacomed, IFRMP 23, Rouen University Medical School and Rouen Hospital, France.
authors.forename: R
authors.initials: R
authors.lastname: Joannides
authors.forename: V
authors.initials: V
authors.lastname: Richard
authors.forename: W E
authors.initials: WE
authors.lastname: Haefeli
authors.forename: A
authors.initials: A
authors.lastname: Benoist
authors.forename: L
authors.initials: L
authors.lastname: Linder
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: C
authors.initials: C
authors.lastname: Thuillez
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects*; D004548:Elasticity; D005260:Female; D006801:Humans; D008297:Male; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D017534:Radial Artery / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000109:Acetylcholine