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Research ArticleCardiovascular

Impaired Function of Prejunctional Adenosine A1 Receptors Expressed by Perivascular Sympathetic Nerves in DOCA-Salt Hypertensive Rats

Sutheera Sangsiri, Hua Dong, Gregory M. Swain, James J. Galligan and Hui Xu
Journal of Pharmacology and Experimental Therapeutics April 2013, 345 (1) 32-40; DOI: https://doi.org/10.1124/jpet.112.199612
Sutheera Sangsiri
Departments of Pharmacology and Toxicology (S.S., J.J.G., H.X.), Chemistry (H.D., G.M.S.), and the Neuroscience Program (G.M.S., J.J.G.), Michigan State University, East Lansing, Michigan
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Hua Dong
Departments of Pharmacology and Toxicology (S.S., J.J.G., H.X.), Chemistry (H.D., G.M.S.), and the Neuroscience Program (G.M.S., J.J.G.), Michigan State University, East Lansing, Michigan
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Gregory M. Swain
Departments of Pharmacology and Toxicology (S.S., J.J.G., H.X.), Chemistry (H.D., G.M.S.), and the Neuroscience Program (G.M.S., J.J.G.), Michigan State University, East Lansing, Michigan
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James J. Galligan
Departments of Pharmacology and Toxicology (S.S., J.J.G., H.X.), Chemistry (H.D., G.M.S.), and the Neuroscience Program (G.M.S., J.J.G.), Michigan State University, East Lansing, Michigan
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Hui Xu
Departments of Pharmacology and Toxicology (S.S., J.J.G., H.X.), Chemistry (H.D., G.M.S.), and the Neuroscience Program (G.M.S., J.J.G.), Michigan State University, East Lansing, Michigan
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Abstract

Increased sympathetic nervous system activity contributes to deoxycorticosterone acetate (DOCA)-salt hypertension in rats. ATP and norepinephrine (NE) are coreleased from perivascular sympathetic nerves. NE acts at prejunctional α2-adrenergic receptors (α2ARs) to inhibit NE release, and α2AR function is impaired in DOCA-salt rats. Adenosine, an enzymatic ATP degradation product, acts at prejunctional A1 adenosine receptors (A1Rs) to inhibit NE release. We tested the hypothesis that prejunctional A1R function is impaired in sympathetic nerves supplying mesenteric arteries (MAs) and veins (MVs) of DOCA-salt rats. Electrically evoked NE release and constrictions of blood vessels were studied in vitro with use of amperometry to measure NE oxidation currents and video microscopy, respectively. Immunohistochemical methods were used to localize tyrosine hydroxylase (TH) and A1Rs in perivascular sympathetic nerves. TH and A1Rs colocalized to perivascular sympathetic nerves. Adenosine and N6-cyclopentyl-adenosine (CPA, A1R agonist) constricted MVs but not MAs. Adenosine and CPA (0.001–10 µM) inhibited neurogenic constrictions and NE release in MAs and MVs. DOCA-salt arteries were resistant to adenosine and CPA-mediated inhibition of NE release and constriction. The A2A adenosine receptor agonist CGS21680 (C23H29N7O6.HCl.xH2O) (0.001–0.1 μM) did not alter NE oxidation currents. We conclude that there are prejunctional A1Rs in arteries and both pre- and postjunctional A1Rs in veins; thus, adenosine selectively constricts the veins. Prejunctional A1R function is impaired in arteries, but not veins, from DOCA-salt rats. Sympathetic autoreceptor dysfunction is not specific to α2ARs, but there is a more general disruption of prejunctional mechanisms controlling sympathetic neurotransmitter release in DOCA-salt hypertension.

Footnotes

    • Received September 1, 2012.
    • Accepted February 7, 2013.
  • This work was supported by funding from Thai Government Science and Technology Scholarship [Grant TS-146]; an American Heart Association, Mid-West Affiliate predoctoral fellowship [Grant 09PRE2180037] (to S.S.); and the National Institutes of Health National Heart, Lung, and Blood Institute [Grants HL070687 (to J.J.G.) and HL84258 (to G.M.S.)].

  • dx.doi.org/10.1124/jpet.112.199612.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 345 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 345, Issue 1
1 Apr 2013
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Research ArticleCardiovascular

A1R Inhibition of Norepinephrine Release

Sutheera Sangsiri, Hua Dong, Gregory M. Swain, James J. Galligan and Hui Xu
Journal of Pharmacology and Experimental Therapeutics April 1, 2013, 345 (1) 32-40; DOI: https://doi.org/10.1124/jpet.112.199612

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Research ArticleCardiovascular

A1R Inhibition of Norepinephrine Release

Sutheera Sangsiri, Hua Dong, Gregory M. Swain, James J. Galligan and Hui Xu
Journal of Pharmacology and Experimental Therapeutics April 1, 2013, 345 (1) 32-40; DOI: https://doi.org/10.1124/jpet.112.199612
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