Peroxynitrite versus nitric oxide in early diabetes.
BACKGROUND
Peroxynitrite is a toxic compound formed during the inactivation of nitric oxide (NO) by the superoxide anion. The physiologic significance of this pathway of NO metabolism has never been documented in vivo. Because peroxynitrite provides a pathway for the inactivation of NO we postulated that peroxynitrite's correlation with physiologic parameters would be the opposite of those associated with NO, which is a vasodilator and suppresses sudomotor function. We assessed the significance of peroxynitrite by comparing its associations with blood pressure (BP) and sudomotor responses with those of NO.


METHODS
Thirty-seven patients with type 1 diabetes enrolled in a longitudinal study of oxidative stress. Nitric oxide was assessed from nitrite and nitrate (collectively NOx) and peroxynitrite was assessed from the nitrotyrosine (nTy) content of protein.


METHODS
nTy was 13.3 +/- 2.0 micromol/L in the control subjects and 26.8 +/- 4.4 micromol/L, 26.1 +/- 4.3 micromol/L, and 32.7 +/- 4.3 micromol/L in the diabetic patients (P <.01) at the time of the first, second, and third evaluations, respectively. Patients with increased nitrotyrosine/tyrosine (nTy/Ty) had higher mean BP than those with low nTy/Ty (81.1 +/- l.9 mm Hg v 75.5 +/- 1.7 at the third evaluation, P <.025). The ratio of nTy/NOx correlated with BP at the first (P <.05), second (P <.05), and third (P <.01) evaluations. Patients with high nTy/Ty had increased sudomotor responses (5.85 +/- 0.75 microL of total sweat) at the third evaluation compared to those with low nTy/Ty (3.32 +/- 0.43 microL, P <.005) and normal controls (3.90 +/- 0.41 microL, P <.05). The associations of nTy with BP and sudomotor responses were the opposite of those with NOx.


CONCLUSIONS
The conversion of NO oxide to peroxynitrite is physiologically significant in humans.
Hoeldtke
Robert D
RD
Department of Medicine, West Virginia University, One Medical Center Drive, PO Box 9159, Morgantown, WV 26506-9159, USA. rhoeldtke@hsc.wvu.edu
Bryner
Kimberly D
KD
McNeill
Daniel R
DR
Hobbs
Gerald R
GR
Baylis
Chris
C
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D001798:Blood Proteins / Q000378:metabolism; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D015588:Observer Variation; D018384:Oxidative Stress / Q000502:physiology; D030421:Peroxynitrous Acid / Q000378:metabolism*; D012720:Severity of Illness Index; D013223:Statistics as Topic
D015415:Biomarkers; D001786:Blood Glucose; D001798:Blood Proteins; D006442:Glycated Hemoglobin; D009569:Nitric Oxide; D030421:Peroxynitrous Acid