Journal
HYPERTENSION
Volume 55, Issue 2, Pages 363-369Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.109.145870
Keywords
endothelium-dependent dilation; aging; NO; tetrahydrobiopterin; neutrophils
Categories
Funding
- National Institutes of Health [AG031617, AG006537, AG013038, AG015897, AG022241, AG000279, RR00051, AG031141, AG029337]
- American Heart Association [0715735Z]
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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 NG-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. (Hypertension. 2010;55:363-369.)
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