title: Heterogenous vasodilator pathways underlie flow-mediated dilation in men and women.
abstract: This study investigated the sex differences in the contribution of nitric oxide (NO) and prostaglandins (PGs) to flow-mediated dilation (FMD). Radial artery (RA) FMD, assessed as the dilatory response to 5-min distal cuff occlusion, was repeated after three separate brachial artery infusions of saline (SAL), N(G)-monomethyl-L-arginine (L-NMMA), and ketorolac (KETO) + L-NMMA in healthy younger men (M; n = 8) and women (W; n = 8). In eight subjects (4 M, 4W) RA FMD was reassessed on a separate day with drug order reversed (SAL, KETO, and L-NMMA + KETO). RA FMD was calculated as the peak dilatory response observed relative to baseline (%FMD) and expressed relative to the corresponding area under the curve shear stress (%FMD/AUC SS). L-NMMA reduced %FMD similarly and modestly (P = 0.68 for sex * trial interaction) in M and W (all subjects: 10.0 ± 3.8 to 7.6 ± 4.7%; P = 0.03) with no further effect of KETO (P = 0.68). However, all sex * trial and trial effects on %FMD/AUC SS for l-NMMA and KETO + l-NMMA were insignificant (all P > 0.20). There was also substantial heterogeneity of the magnitude and direction of dilator responses to blockade. After l-NMMA infusion, subjects exhibited both reduced (n = 14; range: 11 to 78% decrease) and augmented (n = 2; range: 1 to 96% increase) %FMD. Following KETO + l-NMMA, seven subjects exhibited reduced dilation (range: 10 to 115% decrease) and nine subjects exhibited augmented dilation (range: 1 to 212% increase). Reversing drug order did not change the nature of the findings. These findings suggest that RA FMD is not fully or uniformly NO dependent in either men or women, and that there is heterogeneity in the pathways underlying the conduit dilatory response to ischemia.
authors.affiliation: Henry Low Heart Center, Department of Cardiology, Hartford Hospital, Hartford, Connecticut 06102, USA. bparker03@harthosp.org
authors.forename: Beth A
authors.initials: BA
authors.lastname: Parker
authors.forename: Michael E
authors.initials: ME
authors.lastname: Tschakovsky
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Augeri
authors.forename: Donna M
authors.initials: DM
authors.lastname: Polk
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Kiernan
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D020910:Ketorolac / Q000008:administration & dosage; D017078:Laser-Doppler Flowmetry; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D017534:Radial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D012039:Regional Blood Flow; D012737:Sex Factors; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000008:administration & dosage
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D005996:Nitroglycerin; D020910:Ketorolac