Glyceryl trinitrate enhances the adenosine-induced inhibition of platelet responses: a mechanism potentially involved in the in vivo anti-aggregating effects of organic nitrates

Clinical and Experimental Pharmacology & Physiology
G AnfossiM Trovati

Abstract

1. The present study investigated the influence of the organic nitrate glyceryl trinitrate (GTN) on the anti-aggregating effects of adenosine. We determined the effects of adenosine, GTN and their combination on platelet responses in platelet-rich plasma and whole blood, and on intracellular levels of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). 2. Adenosine inhibited the in vitro platelet aggregation in response to different agonists in a dose-dependent way through an elevation of intraplatelet cAMP levels. Effective adenosine concentrations were higher than those detectable under physiological conditions, but very close to levels achieved during myocardial ischaemia or haemorrhagic shock. 3. GTN was able to decrease platelet responses influencing intraplatelet cGMP levels. Furthermore, the drug increased the inhibitory effects of adenosine and enhanced its effects on intraplatelet cAMP levels. 4. The present data provides further evidence that compounds that increase intraplatelet levels of cGMP and cAMP act synergistically on the inhibition of platelet aggregability through the influence of increased cGMP levels on cAMP accumulation. The interplay between GTN and adenosine in t...Continue Reading

References

Aug 1, 1991·Endocrine Reviews·M ContiJ V Swinnen
Jul 5, 1990·The New England Journal of Medicine·J R VaneR M Botting
Jan 1, 1990·Thrombosis Research. Supplement·S MoncadaE A Higgs
Aug 1, 1988·British Journal of Pharmacology·J C HoganA H Henderson
Aug 1, 1985·The Journal of Clinical Investigation·J Loscalzo
Jul 1, 1986·The Journal of Clinical Investigation·F Murad
Jan 1, 1985·Annual Review of Pharmacology and Toxicology·L J Ignarro, P J Kadowitz
Feb 1, 1986·Circulation Research·H V Sparks, H Bardenheuer
Sep 1, 1988·Acta Neurologica Scandinavica·J J Lopez-LozanoH Liaño
Feb 20, 1986·The New England Journal of Medicine·R Ross
Mar 1, 1987·Archives of Internal Medicine·L Kaiser, H V Sparks
May 1, 1974·The Journal of Clinical Investigation·A C FoxB B Silk
May 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·C LondosJ Wolff
Jan 1, 1983·Thrombosis Research. Supplement·L A Harker, R A Kadatz
Mar 15, 1983·Thrombosis Research·T RingC E Larsen
Dec 1, 1983·Regulatory Toxicology and Pharmacology : RTP·P O Nees
May 29, 1980·The New England Journal of Medicine·J Abrams
Mar 1, 1981·The Journal of Clinical Investigation·R I LevinK Tack-Goldman
Feb 1, 1980·Journal of Pharmacological Methods·D C Cardinal, R J Flower

❮ Previous
Next ❯

Citations

Mar 2, 2002·Journal of Diabetes and Its Complications·Mariella Trovati, Giovanni Anfossi
Jun 29, 2004·European Journal of Pharmacology·Tohru NojiHideaki Kusaka
Oct 25, 2007·Platelets·Norbert ZimmermannThomas Hohlfeld
Mar 25, 2017·Brain Sciences·Nathan T FriedMichael L Oshinsky

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antianginal Drugs: Mechanisms of Action

Antianginal drugs, including nitrates, beta-blockers, and calcium channel blockers, are used in the treatment of angina pectoris. Here is the latest research on their use and their mechanism of action.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.