title: White blood cell count and endothelin-1 vasoconstrictor tone in middle-aged and older adults.
abstract: BACKGROUND
  Higher white blood cell (WBC) count is associated with impaired endothelium-dependent vasodilation. However, the influence of higher WBC count on endothelin (ET)-1 vasoconstrictor activity is currently unknown. We tested the hypothesis that adults with elevated WBC count demonstrate enhanced ET-1 system activity.
  
  
  METHODS
  Thirty-four healthy adults were studied: 17 with WBC count < 5.0 × 109cells/L (lower WBC; 9M/8F; age: 53 ± 2 yr) and 17 with WBC count > 5.0 × 109cells/L (higher WBC; 10M/7F; 54 ± 3 yr). Forearm blood flow (FBF) responses to intra-brachial infusion of ET-1 (5 pmol/min for 20 min) and selective ETAreceptor blockade (BQ-123; 100 nmol/min for 60 min) were measured by venous occlusion plethysmography.
  
  
  RESULTS
  The vasoconstrictor response to ET-1 was significantly blunted (∼60%) in the higher WBC group versus the lower WBC group. The FBF responses to selective ETAreceptor blockade were also significantly different (P< 0.05) between the groups. In the lower WBC group, resting FBF increased marginally (∼5%) to BQ-123, whereas the increase in FBF to BQ-123 was significantly greater (∼15%) in higher WBC group. Furthermore, there was a significant relation between WBC count and FBF response to ET-1 (r= -0.43) and BQ-123 (r= 0.41).
  
  
  CONCLUSIONS
  Relative elevations in WBC count in middle-aged and older adults, independent of adiposity and other cardiometabolic risk factors, are associated with enhanced ET-1-mediated vasoconstrictor tone. Elevated ET-1 system activity may be a mechanism linking higher WBC count with increased cardiovascular risk.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, Colorado, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Diehl
authors.forename: Brian R
authors.initials: BR
authors.lastname: Weil
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Desouza
keywords: Endothelin; Vasoconstriction; White blood cell
references.citation: J Intern Med. 1996 May;239(5):435-41
references.pmid: 8642236
references.citation: Hypertension. 2007 Aug;50(2):403-9
references.pmid: 17576858
references.citation: J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S377-9
references.pmid: 11078425
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 May;298(5):R1188-94
references.pmid: 20237301
references.citation: Can J Physiol Pharmacol. 2010 Aug;88(8):777-81
references.pmid: 20725134
references.citation: Clin Chim Acta. 2007 Feb;377(1-2):127-32
references.pmid: 17067564
references.citation: J Am Coll Cardiol. 2004 Nov 16;44(10):1945-56
references.pmid: 15542275
references.citation: JAMA. 1992 Mar 4;267(9):1253-6
references.pmid: 1538564
references.citation: Atherosclerosis. 2005 Aug;181(2):329-38
references.pmid: 16039287
references.citation: Hypertension. 1999 Feb;33(2):753-8
references.pmid: 10024340
references.citation: Circulation. 2000 Sep 19;102(12):1351-7
references.pmid: 10993851
references.citation: Ann Med. 2004;36(2):153-60
references.pmid: 15119835
references.citation: J Inflamm Res. 2012;5:7-11
references.pmid: 22334791
references.citation: Atherosclerosis. 2004 Jan;172(1):1-6
references.pmid: 14709350
references.citation: Hypertension. 2010 Feb;55(2):363-9
references.pmid: 20048194
references.citation: Neurology. 2005 Jun 28;64(12):2121-5
references.pmid: 15985584
references.citation: Clin Sci (Lond). 2009 Apr;116(8):651-8
references.pmid: 18851714
references.citation: Int J Cardiol. 2007 Apr 4;116(3):376-82
references.pmid: 16884793
references.citation: Am J Epidemiol. 2001 Oct 15;154(8):758-64
references.pmid: 11590089
references.citation: Diabetes. 2002 Dec;51(12):3517-23
references.pmid: 12453909
references.citation: Am J Hypertens. 2004 Mar;17(3):233-9
references.pmid: 15001197
references.citation: Obes Res. 1995 Nov;3(6):563-71
references.pmid: 8653533
references.citation: Stroke. 1996 Nov;27(11):2005-11
references.pmid: 8898806
references.citation: Clin Exp Pharmacol Physiol. 1999 Feb;26(2):158-61
references.pmid: 10065339
references.citation: N Engl J Med. 1999 Jan 14;340(2):115-26
references.pmid: 9887164
references.citation: J Am Coll Cardiol. 2000 Nov 1;36(5):1483-8
references.pmid: 11079646
references.citation: J Leukoc Biol. 2007 Jul;82(1):1-15
references.pmid: 17452476