Platelet inhibitory effect of nitric oxide in the human coronary circulation: impact of endothelial dysfunction
Neil P. Andrews, BMBS, MRCPa,
Mohsin Husain, MDa,
Nader Dakak, MDa and
Arshed A. Quyyumi, MD, FRCP, FACCa
a Cardiology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland, USA
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Figure 1 Protocol design. L-NMMA = L-NG monomethyl arginine.
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Figure 2 Changes in coronary sinus platelet cGMP content, coronary blood flow and epicardial diameter during intracoronary infusion of acetylcholine (n = 26). All tests use one-way analysis of variance. cGMP = cyclic guanosine monophosphate.
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Figure 3 Acetylcholine-mediated changes in coronary sinus platelet cGMP content and coronary blood flow in patients with (n = 11) (dashed lines) and those without (n = 15) (solid lines) epicardial coronary constriction with 10–6mol/l acetylcholine. Baseline coronary blood flow (40.7 ± 9 vs. 43.6 ± 8 ml/min, p = 0.8) and platelet cGMP content (0.72 ± 0.1 vs. 0.83 ± 0.2 pmol/109 platelets, p = 0.6) were not significantly different between patients with epicardial constriction compared to those with dilation in response to acetylcholine. Differences between groups by analysis of variance. cGMP = cyclic guanosine monophosphate.
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Figure 4 Changes in coronary sinus platelet cGMP content, coronary blood flow and epicardial diameter during intracoronary acetylcholine (10–6 mol/l) and sodium nitroprusside (40 µg/min) infusions in patients with (n = 19) (shaded bars) and those without (n = 7) (open bars) atherosclerosis or its risk factors. Baseline coronary blood flow (30.7 ± 5 vs. 43.6 ± 7 ml/min), coronary diameter (2.3 ± 0.6 vs 2.2 ± 0.6 mm) and platelet cGMP content (0.76 ± 0.2 vs. 0.79 ± 0.1 pmol/109 platelets) were not significantly different between patients with and those without atherosclerosis or its risk factors, p > 0.2. Open bars = normal; solid bars = atherosclerosis or risk factors. *p < 0.05, **p < 0.02. cGMP = cyclic guanosine monophosphate.
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Figure 5 Percent change in platelet cGMP content during in vitro incubation with acetylcholine, sodium nitroprusside and L-NMMA is shown in open circles. For comparison, the effect of these agonists at estimated intracoronary concentrations achieved during in vivo administration in the normal subjects are shown in closed circles. *p  0.05, **p < 0.001 compared to baseline. cGMP = cyclic guanosine monophosphate; L-NMMA = L-NG monomethyl arginine.
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