To determine differences in A1- and A2-selective adenosine effects on coronary endothelium, isolated rabbit hearts (n = 18) were perfused with erythrocyte-enriched buffer at constant left ventricular volume and physiologic flow rates. After 10-20 minutes of stabilization, the perfusate was changed to contain an A1-selective agonist (N6-cyclopentyladenosine, CPA; high dose, 4.26 X 10-7M or low dose, 10-8M), or an A2-selective agonist ((5'-(N-cyclopropyl) carboxaminoadenosine, CPCA; high dose, 4.45 X 10-6M or low dose 10-7 M). Before and during each treatment period of 1-15 minutes aortic and left ventricular pressures and rates of change were recorded. Hearts were then perfused intravascularly with ruthenium red stain (RR) dissolved in filtered 2.5% glutaraldehyde, and processed by routine electron microscopic methods for ultrastructural examination. Of the hemodynamic parameters measured only aortic pressure increased with CPA, and decreased with CPCA, indicating the expected pharmacologic efficacy at the doses used. However, no observable differences in RR uptake was noted between hearts that received no adenosine agonist and either low- or high-dose CPA. CPCA-treated hearts had noticeable RR uptake into endothelium with both low and high dose levels, with a marked uptake in hearts receiving high doses of this A2 agonist. These results provide direct morphological evidence that supports the concept that endothelial macromolecular uptake is an adenosine A2-mediated process.
| Identifer | oai:union.ndltd.org:pacific.edu/oai:scholarlycommons.pacific.edu:uop_etds-3271 |
| Date | 01 January 1994 |
| Creators | Baker, H. Lane |
| Publisher | Scholarly Commons |
| Source Sets | University of the Pacific |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | University of the Pacific Theses and Dissertations |
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