Related Experiment Videos
Platelet inhibitory effect of nitric oxide in the human coronary circulation: impact of endothelial dysfunction
N P Andrews1, M Husain, N Dakak
1Cardiology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
Insights
Nitric oxide (NO) release in coronary arteries influences platelet activation. Reduced NO’s platelet inhibitory effect in endothelial dysfunction may increase thrombotic risk.
Area of Science:
- Cardiovascular Research
- Endothelial Function
- Platelet Biology
Background:
- Nitric oxide (NO) regulates vascular tone and platelet activity through the cyclic guanosine monophosphate (cGMP) pathway.
- The impact of coronary endothelial dysfunction on human platelet activation remains unclear.
Purpose of the Study:
- To investigate whether in vivo coronary vascular nitric oxide (NO) release modulates platelet activation.
- To assess the relationship between endothelial dysfunction and platelet cGMP levels.
Main Methods:
- Coronary blood flow, epicardial diameter, and coronary sinus platelet cGMP were measured in 26 patients.
- Intracoronary infusions of acetylcholine (ACH), L-NG monomethyl arginine (L-NMMA), and sodium nitroprusside were administered.
Main Results:
- Acetylcholine increased platelet cGMP, but less so in patients with endothelial dysfunction.
- Patients with atherosclerosis or risk factors showed a blunted cGMP response to ACH compared to healthy individuals.
- L-NMMA reduced platelet cGMP more significantly in patients with endothelial dysfunction.
Conclusions:
- Basal and stimulated nitric oxide (NO) release modulates platelet cyclic guanosine monophosphate (cGMP) levels.
- The platelet inhibitory effect of NO is diminished in individuals with endothelial dysfunction.
- This reduction may contribute to increased thrombotic event risk in these patients.
Objectives:
We sought to determine whether coronary vascular nitric oxide (NO) release in vivo modulates platelet activation.
Background:
Nitric oxide modulates vasodilator tone and platelet activity via the cyclic guanosine monophosphate (cGMP) pathway, but whether coronary endothelial dysfunction influences platelet activation in humans is unknown.
Methods:
In 26 patients, we measured coronary blood flow, epicardial diameter and coronary sinus platelet cGMP content during intracoronary infusions of acetylcholine (ACH), L-NG monomethyl arginine (L-NMMA) and sodium nitroprusside.
Results:
Acetylcholine increased platelet cGMP content (p = 0.013), but its magnitude was lower in patients with endothelial dysfunction; thus, patients with epicardial constriction with ACH had a 7 +/- 6%, p = ns change compared with a 32 +/- 13%, p = 0.05 increase in platelet cGMP in those with epicardial dilation. Similarly, patients with atherosclerosis or its risk factors had a smaller increase (9 +/- 6%) compared with those having normal coronary arteries without risk factors (51 +/- 22%, p = 0.019). L-NG monomethyl arginine decreased platelet cGMP content to a greater extent in patients with epicardial dilation with ACH (- 15 +/- 7%, p = 0.06) compared to those with constriction (+5 +/- 6% change, p = 0.5). Sodium nitroprusside produced a similar increase in platelet cGMP content in patients with and without endothelial dysfunction (p = 0.56). The effects of sodium nitroprusside, but not ACH or L-NMMA, were reproduced in vitro.
Conclusions:
Platelet cGMP levels can be modulated by basal and stimulated release of NO. The platelet inhibitory effect of NO is reduced in patients with endothelial dysfunction, which may explain their increased risk from thrombotic events and the improved survival associated with strategies designed to improve vascular function.