Nitric oxide regulates local arterial distensibility in vivo.
BACKGROUND
Arterial stiffness is an important determinant of cardiovascular risk. Several lines of evidence support a role for the endothelium in regulating arterial stiffness by release of vasoactive mediators. We hypothesized that nitric oxide (NO) acting locally regulates arterial stiffness in vivo, and the aim of this experiment was to test this hypothesis in an ovine hind-limb preparation.


RESULTS
All studies were conducted in anesthetized sheep. Pulse wave velocity (PWV) was calculated by the foot-to-foot methodology from 2 pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA) increased iliac PWV significantly, by 3+/-2% (P<0.01). Infusion of acetylcholine and glyceryl trinitrate reduced PWV significantly, by 6+/-4% (P=0.03) and 5+/-2% (P<0.01), respectively. Only the effect of acetylcholine, however, was significantly inhibited during coinfusion of L-NMMA (P=0.03). There was no change in systemic arterial pressure throughout the studies. Importantly, infusion of L-NMMA or acetylcholine distal to the common iliac artery (via the sheath) did not affect PWV.


CONCLUSIONS
These results demonstrate, for the first time, that basal NO production influences large-artery distensibility. In addition, exogenous acetylcholine and glyceryl trinitrate both increase arterial distensibility, the former mainly through NO production. This may help explain why conditions that exhibit endothelial dysfunction are also associated with increased arterial stiffness. Therefore, reversal of endothelial dysfunction or drugs that are large-artery vasorelaxants may be effective in reducing large-artery stiffness in humans, and thus cardiovascular risk.
Wilkinson
Ian B
IB
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. ibw20@cam.ac.uk
Qasem
Ahmed
A
McEniery
Carmel M
CM
Webb
David J
DJ
Avolio
Albert P
AP
Cockcroft
John R
JR
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology*; D004548:Elasticity; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005121:Extremities / Q000098:blood supply; D006439:Hemodynamics; D007083:Iliac Artery / Q000187:drug effects / Q000502:physiology; D007261:Infusions, Intra-Arterial; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D012756:Sheep; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D000109:Acetylcholine