Wallace, Ignarro & Fiorucci - 1
Potential Cardioprotective Actions of Nitric Oxide-Releasing Aspirin
John L. Wallace1, Louis J. Ignarro2 & Stefano Fiorucci3
1Department
of Pharmacology & Therapeutics, University of Calgary, Calgary,
Alberta, Canada; 2Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California, USA; 3Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Short Title:
Cardioprotection with NO-Aspirin
Acknowledgements:
Dr. Wallace is an Alberta Heritage Foundation for Medical Research Senior Scientist.
Correspondence:
Prof. J.L. Wallace Department of Pharmacology & Therapeutics University of Calgary Calgary, Alberta, T2N 4N1, CANADA Tel: 403-220-4539
FAX: 403-270-3353 E-mail:
[email protected]
Wallace, Ignarro & Fiorucci - 2
Preface
The use of low doses of aspirin on a daily basis has increased tremendously in the past 20 years, based on observations that it can significantly reduce the risk of heart attacks and strokes. However, aspirin can also cause severe damage to the stomach. A modified version of aspirin, which releases the chemical nitric oxide, has been developed that appears to offer significant advantages over its 100 year old parent; namely, improved protection for the heart without the untoward effects on the stomach.
Wallace, Ignarro & Fiorucci - 3
Background
From its humble beginnings as a better tasting alternative to salicylic acid, aspirin has become one of the most widely used drugs over the past century (1). In the latter part of the 20th century, the use of aspirin for the prevention of diseases such as myocardial infarction, stroke and cancer gained wide attention. The evidence for the efficacy of aspirin in long-term prophylaxis of myocardial infarction and stroke is quite convincing (2-6), such effects being related to its ability to irreversibly inhibit thromboxane production by platelets (and therefore reduce platelet aggregation) (7). Low doses of ASA (