Inhibition of basal nitric oxide synthesis increases aortic augmentation index and pulse wave velocity in vivo.
OBJECTIVE
To investigate the role of basal nitric oxide (NO) production in regulating large artery stiffness in vivo.


METHODS
Incremental doses of the NO synthase inhibitor L-N(G)-monomethyl arginine (LNMMA: 0.1, 0.3, 1.0 and 3.0 mg kg-1 min-1) or placebo were infused in eight healthy men. Arterial stiffness was assessed noninvasively by pulse wave analysis.


RESULTS
Compared with placebo, infusion of LNMMA led to a dose-dependent increase in mean arterial pressure, peripheral vascular resistance, and aortic and systemic arterial stiffness. There was an accompanying reduction in heart rate and cardiac index. The highest dose of LNMMA resulted in an increase of 25% in AIx (95% confidence limits; 12, 38) and of 16 mmHg in mean arterial pressure (9, 23) compared with infusion of saline.


CONCLUSIONS
These data indicate functional regulation of large artery stiffness in vivo by NO, and may provide new therapeutic strategies for cardiovascular risk reduction.
Wilkinson
Ian B
IB
Clinical Pharmacology Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, UK. ibw20@cam.ac.uk
MacCallum
Helen
H
Cockcroft
John R
JR
Webb
David J
DJ
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D017534:Radial Artery / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase