Relative participation of adenosine and endothelium derived mediators in coronary reactive hyperemia in the dog.
The metabolites that mediate coronary reactive hyperemia have not been definitely identified. Although adenosine and endothelium derived substances seem to be involved, their relative contributions have not been defined yet. In the canine coronary circulation, we studied the relative participation of adenosine, nitric oxide and prostacyclin in reactive hyperemia, by measuring the changes produced by interfering with the synthesis or action of these metabolites. The dose-response curve for flow changes vs intracoronary administration of adenosine was displaced to the right after the inhibition of nitric oxide synthesis with N-omega-nitro-L-arginine, revealing that nitric oxide release partly mediates the vasodilator action of adenosine. The inhibition of PGI-2 synthesis with indomethacin did not modify reactive hyperemia. Interference with adenosine action, by administration of adenosine deaminase plus theophylline, decreased reactive hyperemia by 31.0 +/- 4.0% (p < 0.001). Inhibition of nitric oxide synthesis decreased reactive hyperemia by a larger (p < 0.005) magnitude, 41.0 +/- 3.9% (p < 0.001), revealing the existence of other stimuli for nitric oxide release in reactive hyperemia besides adenosine. Simultaneous inhibition of nitric oxide and PGI-2 syntheses and of adenosine action reduced reactive hyperemia, but the effect was not additive, reaching 49.5 +/- 4.5% of control. Since nitric oxide and adenosine are the most important mediators in reactive hyperemia so far described, our results suggest that other metabolites, acting directly or through mediators other than adenosine or nitric oxide, are responsible for about 50% of coronary reactive hyperemia.
Macho
P
P
Departamento de Medicina Experimental, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Domenech
R
R
Penna
M
M
D000241:Adenosine / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D010975:Platelet Aggregation Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D011464:Epoprostenol; D000241:Adenosine