Inhibition of Platelet Function by Organic Nitrate Vasodilators

Overview

• Primary Focus: Investigation of the effects of organic nitrate vasodilators on platelet function, relevant to coronary artery disease.
• Organic Nitrates Studied: Nitroglycerin, isosorbide dinitrate.

Key Findings

• Inhibition of Platelet Aggregation:
  • Inhibited aggregation with collagen, epinephrine, arachidonate, and ionophore.
  • Blocked both primary and secondary aggregation in response to ADP.
• Detailed Study on Nitroglycerin:
  • Reversible inhibitory effect.
  • Effect not dependent on external calcium concentration.
  • Inhibited arachidonic acid oxygenation.
  • Not associated with increased intracellular cyclic AMP.

Mechanism and Implications

• The generalized inhibition of platelet function by nitroglycerin may contribute to its beneficial effects in myocardial ischemia.
• May reduce platelet reactivity in the coronary circulation.

Supporting Information

• Grants and Support:
  • Supported by NIH Grants HL17513 and HL23088.
  • Contributions from the Medical Foundation, Inc., Boston, and the American Heart Association.
• Awards:
  • R.W.A. and R.I.H. received NIH Research Career Development Awards HL00332 and HL00236, respectively.

Conclusion

• Organic nitrate vasodilators like nitroglycerin have a significant inhibitory effect on platelet function, which may play a role in their therapeutic benefits in conditions like myocardial ischemia.