Related Experiment Videos
Inosine transiently decreases coronary flow but potentiates vasodilation by adenosine
1Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
Insights
Inosine enhances adenosine-induced vasodilation and acts as a coronary vasodilator, though it may also cause transient vasoconstriction. This study investigated inosine
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Nucleoside Metabolism
Background:
- Adenosine is a key regulator of coronary blood flow.
- Inosine's role in modulating adenosine's effects and its direct impact on coronary circulation are not fully understood.
Purpose of the Study:
- To investigate the interaction between inosine and adenosine in the isolated rat heart.
- To determine the direct effects of inosine on coronary hemodynamics and adenosine metabolism.
Main Methods:
- Isolated rat heart preparations were used.
- Intracoronary administration of inosine, adenosine, adenosine deaminase, and 8-phenyltheophylline was performed.
- Measurements included heart rate, developed tension, coronary flow, and effluent adenosine concentration.
Main Results:
- Inosine potentiated adenosine-induced vasodilation and increased coronary effluent adenosine.
- Inosine inhibited exogenous adenosine uptake and breakdown.
- Inosine exhibited concentration-dependent sustained vasodilation, but also a transient vasoconstriction.
- The transient vasoconstrictive effect of inosine was independent of adenosine signaling.
Conclusions:
- Inosine potentiates adenosine-mediated vasodilation in the coronary circulation.
- Inosine acts as a coronary vasodilator, but also possesses a transient vasoconstrictor effect.
- Inosine influences endogenous adenosine levels and metabolism.
Abstract:
To test whether inosine interferes with the action of adenosine, we investigated the effects of intracoronary administration of inosine, adenosine, 8-phenyltheophylline, and adenosine deaminase on isolated rat heart. Inosine did not change heart rate or developed tension but increased the effluent adenosine concentration. Inosine also decreased exogenous adenosine uptake and breakdown. After the start of the inosine infusion (20 microM), a transient 30% decrease of coronary flow took place within 0.5 min. The nucleoside caused sustained vasodilation, dependent on the concentration (30-400 microM). After the infusion we observed a transient vasodilation. A nonvasoactive inosine concentration (10 microM) combined with an adenosine concentration that increased flow by 60% (0.1 microM) raised vasodilation by another 60%. Infusion of adenosine, adenosine deaminase, or 8-phenyltheopylline did not influence the inosine-induced transient decrease of flow, suggesting that this decrease is independent of adenosine and its receptor. We conclude that inosine 1) potentiates the vasodilation induced by adenosine and 2) is a coronary vasodilator but probably also a vasoconstrictor.