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Cardiovascular effects of nucleoside analogs
Annals of the New York Academy of Sciences
|August 8, 1975
Summary
Novel adenosine-5'-carboxylic acid derivatives increase coronary oxygen levels and blood flow. These compounds act directly on adenosine receptors, offering a prolonged effect due to resistance to metabolic degradation.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Adenosine plays a crucial role in cardiovascular regulation.
- Understanding adenosine receptor agonists is vital for developing new cardiovascular therapies.
Purpose of the Study:
- To investigate the cardiovascular effects of short-chain aliphatic esters and amides of adenosine-5 ahydrochloride.
- To elucidate the mechanism of action and metabolic stability of these novel adenosine derivatives.
Main Methods:
- Intravenous administration of adenosine derivatives in dogs and spontaneously hypertensive rats.
- Measurement of coronary sinus oxygen tension (PO2), coronary flow, blood pressure, and heart rate.
- In vitro enzymatic assays using adenosine deaminase and adenylate deaminase.
Main Results:
- Adenosine derivatives significantly increased coronary sinus PO2 and coronary flow, with amides being more potent.
- Hypotension and tachycardia were observed with amides; hypotensive effects were also seen in hypertensive rats.
- Aminophylline, an adenosine receptor antagonist, blocked the coronary flow increase.
- Compounds showed poor substrate potential for adenosine and adenylate deaminase in vitro, suggesting metabolic stability.
Conclusions:
- Adenosine-5 ahydrochloride derivatives act directly on adenosine receptors.
- Their resistance to enzymatic degradation contributes to a prolonged duration of action.
- These compounds represent a promising class for cardiovascular drug development.