Abstract:
:Adenosine, a vasodilator metabolite, is often produced in tissues where the demand for oxygen exceeds the supply. We have recently demonstrated in isolated cannulated arterioles that adenosine and its metabolite, inosine, can also cause vasoconstriction by stimulation of mast cells. Secondary release of histamine and thromboxane is responsible for the inosine-induced constriction in vivo. In the present study, we explored the vasomotor effects of adenosine in vivo and investigated the role of the A3 adenosine receptor in mediating vasoconstriction. In vivo, local application of adenosine (10-6 to 10-4 mol/L) to arterioles consistently caused dose-dependent vasodilation. A fraction of arterioles, however, exhibited a biphasic response, with constriction following dilation. This, too, was dose dependent; 37% of arterioles constricted by 12.7 +/- 4.3% of the initial diameter in response to 10-4 mol/L adenosine. In the presence of 8-(p-sulfophenyl)theophylline (8-SPT), an antagonist of A1 and A2 adenosine receptors, dilation in response to the same dose of adenosine was reduced, and constriction was enhanced; 85% of the tested arterioles constricted by -44.3 +/- 6.0% of the initial diameter. The A3 adenosine receptor has been shown to facilitate mediator release from mast cells, and its role was also examined. N6-(3-Iodo-4-aminobenzyl)adenosine (I-ABA), an agonist of A1 and A3 adenosine receptors, produced dose-dependent vasoconstriction. 1,3-Dipropyl-8-(4-acrylate)phenylxanthine (BW-A1433), an antagonist of A1, A2, and A3 receptors, significantly reduced the vasoconstrictor response to adenosine, which was unmasked during treatment with 8-SPT. In addition, both adenosine and I-ABA stimulated mast cell uptake of ruthenium red, indicating degranulation. The I-ABA-induced constriction was abolished by combined histamine and thromboxane receptor antagonists. We conclude that adenosine can cause vasoconstriction in vivo, which is often masked by A2 receptor-mediated vasodilation. Mast cells are stimulated in the course of the response, and the A3 adenosine receptor is involved in mediating constriction.
journal_name
Circ Resjournal_title
Circulation researchauthors
Shepherd RK,Linden J,Duling BRdoi
10.1161/01.res.78.4.627subject
Has Abstractpub_date
1996-04-01 00:00:00pages
627-34issue
4eissn
0009-7330issn
1524-4571journal_volume
78pub_type
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更新日期:2007-12-07 00:00:00
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更新日期:2009-07-02 00:00:00
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pub_type: 杂志文章
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更新日期:1989-04-01 00:00:00
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doi:10.1161/01.res.42.6.821
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更新日期:1976-06-01 00:00:00
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更新日期:2003-04-04 00:00:00
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更新日期:1981-05-01 00:00:00
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更新日期:2001-01-19 00:00:00
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更新日期:1997-11-01 00:00:00
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更新日期:1997-06-01 00:00:00
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更新日期:1995-03-01 00:00:00