Impaired vasoreactivity despite an increase in plasma nitrite in patients with abdominal aortic aneurysms.
OBJECTIVE
This investigation was designed to determine whether differences in vasoreactivity occur in patients with abdominal aortic aneurysms (AAAs) as compared with patients with peripheral arterial occlusive disease (PAOD) or individuals (controls) without known vascular disease.


METHODS
Brachial artery vasoreactivity was assessed in a blinded fashion, after endothelium-dependent (ED) and endothelium-independent (EI) flow-mediated vasodilation, in age-matched, male patients with AAAs (n = 11) or PAOD (n = 9) or in controls (n = 10). There were no significant differences in prestudy systolic or diastolic blood pressure, body mass index, or antilipidemic medications among the groups studied. Exclusion criteria included diabetes and tobacco use within 3 months. Quantitative ultrasound scan measurements of brachial artery diameters were performed at rest and after either forearm ischemia (ED) or administration of 0.4 mg sublingual nitroglycerin (EI). Plasma nitric oxide (NO(X) = NO(2) + NO(3)) was measured with the Saville assay. Asymmetric dimethylarginine, an endogenous inhibitor of NO(X) synthase, was measured with liquid chromatography.


RESULTS
Initial brachial artery diameters were not significantly different among the groups studied (4.85 +/- 0.18 mm for AAA group, 4.82 +/- 0.17 mm for PAOD group, 4.68 +/- 0.20 mm for controls). ED and EI vasodilation was significantly less (P =.02 and.03, respectively) in the AAA group (-1.71 +/- 1.52 and 8.33 +/- 1.13, respectively) when compared with the controls (2.96 +/- 1.04 and 13.88 +/- 2.16, respectively). However, plasma NO(X) was significantly increased (P =.01) in the AAA group (7.86 +/- 0.85 micromol/L) as compared with both controls (5.13 +/- 0.63 micromol/L) and PAOD (4.85 +/- 0.46 micromol/L). Asymmetric dimethylarginine levels were decreased in the AAA group (0.34 +/- 0.05 micromol/L) as compared with the PAOD group (0.46 +/- 0.09 micromol/L). No correlation existed between aneurysm size and ED or EI vasodilation or plasma NO(X).


CONCLUSIONS
This study is the first to document a divergence between ED and EI vasoreactivity and systemic NO metabolites in patients with AAAs. It is speculated that a dysfunctional vessel wall response, rather than a lack of NO, may be important in the pathogenesis of AAAs.
Knipp
Brian S
BS
Jobst Vascular Research Laboratories, Section of Vascular Surgery, Department of Surgery, Division of Cardiology, University of Michigan Medical Center, Ann Arbor 48109-0329, USA.
Peterson
David A
DA
Rajagopalan
Sanjay
S
Kehrer
Christine
C
Ford
John W
JW
D'Alecy
Louis G
LG
Whitesall
Steven E
SE
Eagleton
Matthew J
MJ
Wakefield
Thomas W
TW
Henke
Peter K
PK
Jacobs
Lloyd A
LA
Greenfield
Lazar J
LJ
Stanley
James C
JC
Upchurch
Gilbert R
GR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000150:complications; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000150:complications; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008297:Male; D008824:Michigan; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood*
D009573:Nitrites; D009569:Nitric Oxide