Adenosine elicits an eNOS-independent reduction in arterial blood pressure in conscious mice that involves adenosine A2A receptors.
OBJECTIVE
Adenosine plays an important role in the regulation of heart rate (HR) and vascular reactivity. However, the mechanisms underlying the acute effect of adenosine on arterial blood pressure in conscious mice are unclear. Therefore, this study investigated the effect of the nucleoside on mean arterial blood pressure (MAP) and HR in conscious mice.


METHODS
Chronic indwelling catheters were placed in C57Bl/6J (WT) and endothelial nitric oxide synthase knockout (eNOS(-/-)) mice for continuous measurements of MAP and HR. Using PCR and myograph analysis, involvement of adenosine receptors was investigated in human and mouse renal blood vessels.


RESULTS
Bolus infusion of 0.5 mg kg(-1) adenosine elicited significant transient decreases in MAP (99.3 ± 2.3 to 70.4 ± 4.5 mmHg) and HR (603.2 ± 18.3 to 364.3 ± 49.2 min(-1)), which were inhibited by the A(2A) receptor antagonist ZM 241385. Activation of adenosine A(2A) receptors with CGS 21680 (0.02 mg kg(-1)) caused a significant reduction in MAP from 99.6 ± 1.2 to 73.1 ± 3.6 mmHg accompanied by tachycardia (610.5 ± 9.3 to 677.5 ± 9.5 min(-1)). The reduction in MAP observed after adenosine or CGS 21680 administrations was not significantly different in WT and eNOS(-/-) mice. In isolated human and mouse intrarenal arteries, adenosine caused a relaxation dependent on A(2A) adenosine receptor activation. A(2A) receptors were present in both human and mouse arteries whereas A(1) and A(2B) receptors were only present in mouse arteries.


CONCLUSIONS
In conclusion, acute adenosine administration and selective stimulation of adenosine A(2A) receptors results in an immediate, transient eNOS-independent reduction in MAP. A(2A) receptor activation causes relaxation of human and mouse arteries.
Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
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H
Andersen
M G
MG
Jaff
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D
Høgh
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P
Vanhoutte
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PB
Hansen
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003243:Consciousness; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D043705:Receptor, Adenosine A2A; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000241:Adenosine