title: Vascular endothelial function is related to white blood cell count and myeloperoxidase among healthy middle-aged and older adults.
abstract: Endothelium-dependent dilation (EDD) is impaired with aging, but there is significant variability among healthy middle-aged and older adults. We tested the hypothesis that EDD is related to white blood cell (WBC) count in healthy men and women aged 55 to 75 years (n=48) who have a WBC count within the clinically normal range. The peak forearm blood flow response to intrabrachial artery infusion of acetylcholine was inversely related to WBC count (r=-0.38; P=0.004) and was 34% smaller in subjects with higher versus lower WBC count (more versus less than the median of 5.0x10(9) cells per liter; P=0.001). Vascular smooth muscle responsiveness to NO (peak forearm blood flow response to sodium nitroprusside) was inversely related to WBC count (r=-0.30; P=0.02) but did not fully explain the associations with EDD. Inhibition of NO with N(G)-monomethyl-L-arginine reduced EDD in subjects with lower (-56%; P=0.01) but not higher WBC count. Tetrahydrobiopterin selectively improved EDD in subjects with higher WBC count (+35%; P=0.01) by increasing NO bioavailability. EDD was related (P<0.05) to neutrophil, eosinophil, and monocyte but not lymphocyte or basophil counts. Myeloperoxidase, which is secreted by neutrophils and monocytes, consumes NO and produces molecules that oxidize tetrahydrobiopterin, was inversely related to EDD (r=-0.35; P=0.02), and was 42% higher in subjects with a higher WBC count (P=0.02). No other factors contributed to the relation between EDD and WBC count. Among healthy middle-aged and older adults, impaired EDD is related to higher neutrophil, eosinophil, and monocyte-based WBC count mediated by reduced responsiveness to NO and increased myeloperoxidase-associated reductions in tetrahydrobiopterin and NO bioavailability.
authors.affiliation: Department of Integrative Physiology, University of Colorado, Boulder, Colo 80309, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Walker
authors.forename: Sara Marian
authors.initials: SM
authors.lastname: Seibert
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.forename: Gary L
authors.initials: GL
authors.lastname: Pierce
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D001783:Blood Flow Velocity; D001795:Blood Pressure Determination; D016022:Case-Control Studies; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006304:Health Status; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D009195:Peroxidase / Q000097:blood / Q000378:metabolism*; D011336:Probability; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D009195:Peroxidase; D000109:Acetylcholine