title: Platelet nitrate responsiveness in fasting and postprandial type 2 diabetes.
abstract: Vascular responsiveness to exogenous nitrates in type 2 diabetes (T2DM) is attenuated in brachial and coronary vessels. We determined platelet responsiveness to nitric oxide (NO) in T2DM and control subjects. We examined whether the postprandial (PP) state affected platelet sensitivity to NO donors in T2DM patients and the extent of correlation between this and measures of oxidative stress, compared to changes in endothelial function. Twelve T2DM subjects were studied fasting and four hours after a test meal and compared with 15 healthy controls. We assessed the inhibitory effects of NO donors on adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Oxidative stress was assessed by lipid-derived free radicals, ex vivo by electron paramagnetic resonance spectroscopy and markers of lipid peroxidation. Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. Results are expressed as (mean +/- SEM). Fasting platelet aggregation was increased in diabetics versus controls (14.86 +/- 1.1 Ohms vs. 10.76 +/- 1.1 Ohms, p < 0.05). Sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) inhibited ADP-induced aggregation by 73.1 +/- 5.9% and 50.3 +/- 7.7% in healthy controls compared to 15.4 +/- 7% and 19.5 +/- 8.2% in T2DM (p < 0.05). Fasting and postprandial inhibition of platelet aggregation with NO donors in T2DM was similar. T2DM patients had higher levels of oxidative stress in the fasting state and postprandially. There were no PP correlations with platelet NO resistance. In conclusion, there is platelet hyporesponsiveness to NO donors (SNP/GTN) in T2DM compared to controls, with increased ADP-induced platelet aggregation. Platelet abnormalities were associated with increased oxidative stress.
authors.affiliation: Wales Heart Research Institute, University of Wales College of Medicine, Cardiff, Wales. RAAnderson@tiscali.co.uk
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.forename: Gethin R
authors.initials: GR
authors.lastname: Ellis
authors.forename: L Marc
authors.initials: LM
authors.lastname: Evans
authors.forename: Keith
authors.initials: K
authors.lastname: Morris
authors.forename: Yuri Y
authors.initials: YY
authors.lastname: Chirkov
authors.forename: John D
authors.initials: JD
authors.lastname: Horowitz
authors.forename: Simon K
authors.initials: SK
authors.lastname: Jackson
authors.forename: Alan
authors.initials: A
authors.lastname: Rees
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Lewis
authors.forename: Michael P
authors.initials: MP
authors.lastname: Frenneaux
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001916:Brachial Artery / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D005215:Fasting; D005260:Female; D005609:Free Radicals / Q000097:blood; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019518:Postprandial Period; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D005609:Free Radicals; D009566:Nitrates; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D000244:Adenosine Diphosphate; D005996:Nitroglycerin