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Functional role of intravascular coronary endothelial adenosine receptors
E Balcells1, J Suarez, R Rubio
1Department of Physiology, School of Medicine, University of Virginia, Charlottesville 22908.
Insights
Intravascular adenosine, confined to blood vessels using microspheres, impacts heart function and metabolism. This suggests endothelial purine receptors release messengers regulating cardiac cells.
Area of Science:
- Cardiovascular Physiology
- Endothelial Biology
- Pharmacology
Background:
- The endothelium's low permeability to adenosine limits its intravascular effects.
- Endogenous adenosine plays a role in regulating vascular and cardiac function.
- Previous studies suggest adenosine may act within the capillary lumen.
Purpose of the Study:
- To investigate the physiological effects of intravascularly confined adenosine agonists.
- To determine if adenosine can exert actions from within the capillary lumen.
- To explore the role of endothelial purine receptors in mediating adenosine's effects.
Main Methods:
- Coupling adenosine agonists (ADAC, NOA) to carboxylated latex microspheres (0.07 microns) for intravascular confinement.
- Sustained infusion of microsphere-agonist complexes into isolated saline-perfused guinea pig hearts.
- Assessing effects on coronary vascular resistance, cardiac contractility, rhythm, AV transmission, and glycolytic flux.
- Utilizing control microspheres and adenosine antagonist (sulphophenyltheophylline) to confirm specificity.
Main Results:
- Infusion of microsphere-bound adenosine agonists decreased coronary vascular resistance.
- Significant reductions in ventricular contraction, spontaneous rhythm, and AV transmission were observed.
- Glycolytic flux was inhibited, indicating metabolic effects.
- Responses were reversible and specific, as control microspheres had no effect and the antagonist blocked the actions.
Conclusions:
- Selective activation of intravascular coronary purine receptors influences cardiac function and metabolism.
- Endothelial cells may release bioactive messengers in response to intravascular adenosine.
- These messengers regulate vascular and cardiac cell function and metabolism.
Abstract:
The endothelium is relatively 'impermeable' to adenosine. In addition, infusion of adenosine deaminase and transient infusion of large size adenosine agonists (molecular weight 100 kD) which are confined to the intravascular space depress effects of endogenous adenosine and retain physiologic activity respectively. Accordingly, the concept that intravascular adenosine may exert some of its action on the capillary lumen was tested by coupling the agonists: N6-([aminoethylamino]carbonyl)methylphenyladenosine (ADAC) and N6-octylamine adenosine (NOA) to carboxylated latex microspheres (0.07 microns diameter); thus, insuring their intravascular confinement. Our results demonstrated that sustained infusion of these particles into isolated saline perfused guinea pigs hearts caused a decrease in coronary vascular resistance, ventricular contraction, spontaneous ventricular rhythm, inhibition of auricular ventricular transmission and glycolytic flux. These effects were reversible and specific since microspheres without purines had no effect and the adenosine antagonist sulphophenyltheophylline blocked these responses. Furthermore, the effects were not the result that during the passage of the sphere-agonist complex through the heart the covalent bond hydrolyzed, releasing free agonist. Our data indicate that selective activation of intravascular coronary purine receptors may cause the release of endothelial bioactive messengers that regulate the function and metabolism of vascular and cardiac cells.