title: Pulse-wave analysis: clinical evaluation of a noninvasive, widely applicable method for assessing endothelial function.
abstract: Current methods for assessing vasomotor endothelial function are impractical for use in large studies. We tested the hypothesis that pulse-wave analysis (PWA) combined with provocative pharmacological testing might provide an alternative method. Radial artery waveforms were recorded and augmentation index (AIx) was calculated from derived aortic waveforms. Thirteen subjects received sublingual nitroglycerin (NTG), inhaled albuterol, or placebo. Twelve subjects received NTG, albuterol, and placebo separately during an infusion of N(G)-monomethyl-L-arginine (LNMMA) or norepinephrine. Twenty-seven hypercholesterolemic subjects and 27 controls received NTG followed by albuterol. Endothelial function was assessed by PWA and forearm blood flow in 27 subjects. Albuterol and NTG both significantly and repeatably reduced AIx (P<0.001). Only the response to albuterol was inhibited by LNMMA (-9.8+/-5.5% vs -4.7+/-2.7%; P=0.02). Baseline AIx was higher in the hypercholesterolemic subjects, who exhibited a reduced response to albuterol (P=0.02) but not to NTG when compared with matched controls. The responses to albuterol and acetylcholine were correlated (r=0.5, P=0.02). Consistent with an endothelium-dependent effect, the response to albuterol was substantially inhibited by LNMMA. Importantly, the response to albuterol was reduced in subjects with hypercholesterolemia and was correlated to that of intra-arterial acetylcholine. This methodology provides a simple, repeatable, noninvasive means of assessing endothelial function in vivo.
authors.affiliation: Clinical Pharmacology Units, University of Cambridge, Addenbrooke's Hospital, Cambridge, England. ibw20@cam.ac.uk
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
authors.forename: Ian R
authors.initials: IR
authors.lastname: Hall
authors.forename: Helen
authors.initials: H
authors.lastname: MacCallum
authors.forename: Isla S
authors.initials: IS
authors.lastname: Mackenzie
authors.forename: Carmel M
authors.initials: CM
authors.lastname: McEniery
authors.forename: Bart J
authors.initials: BJ
authors.lastname: van der Arend
authors.forename: Yae-Eun
authors.initials: YE
authors.lastname: Shu
authors.forename: Laura S
authors.initials: LS
authors.lastname: MacKay
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
authors.forename: John R
authors.initials: JR
authors.lastname: Cockcroft
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003187:Compliance; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010991:Plethysmography / Q000187:drug effects / Q000379:methods; D017534:Radial Artery / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015203:Reproducibility of Results; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine
chemical_list: D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D005996:Nitroglycerin; D000109:Acetylcholine; D000420:Albuterol; D009638:Norepinephrine