Modulation of vascular response by high salt intake depends on the presence or absence of adenosine A2A receptor using A2A AR‐null mice
In: The FASEB Journal ; volume 27, issue S1 ; ISSN 0892-6638 1530-6860, 2013
academicJournal
Zugriff:
High salt (HS) has been shown to modulate adenosine‐induced vascular response through A 2A AR. We hypothesized that HS enhances adenosine‐induced relaxation through cyp‐epoxygenases in the presence of A 2A AR, but exaggerates contraction in the absence of A 2A AR. Organ bath and western blot studies were conducted with 4% (HS) and 0.18% NaCl (NS) diet fed A 2A AR −/− and A 2A AR +/+ mice. Non‐selective adenosine analog (NECA) produced significantly higher relaxation in HS‐A 2A AR +/+ vs. NS‐A 2A AR +/+ , NS & HS‐A 2A AR −/− . Also, CGS 21680, selective A 2A AR agonist, enhanced relaxation in HS‐A 2A AR +/+ vs. NS‐A 2A AR +/+ which was blocked by an EET antagonist (14,15‐EEZE) but not by L‐NAME (NOS inhibitor) and indomethacin (COX inhibitor). NECA induced contraction in NS & HS‐A 2A AR −/− was reversed by A 1 AR antagonist, DPCPX. Also, CCPA, a selective A 1 AR agonist yielded higher contraction in NS & HS‐A 2A AR −/− vs. NS & HS‐A 2A AR +/+ mice. Compared with NS‐A 2A AR +/+ , HS‐A 2A AR +/+ demonstrated upregulation of A 2A AR (60%), cyp2c29 (64%) and downregulation of A 1 AR (17%) & cyp4a (46%). A 1 AR (20 %) & cyp4a (50%) were upregulated and cyp2c29 (54%) was downregulated in HS‐A 2A AR −/− vs. HS A 2A AR +/+ . Our data suggest HS elicited enhanced A 2A AR‐induced relaxation through cyp‐epoxygenases in A 2A AR +/+ is abolished in the A 2A AR −/− , further exaggerating contraction via A 1 AR. Supported (BGF‐WVU, STF‐WVU, HL027339, HL094447, GM31278 & z01 ES025034).
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Modulation of vascular response by high salt intake depends on the presence or absence of adenosine A2A receptor using A2A AR‐null mice
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Autor/in / Beteiligte Person: | Pradhan, Isha ; Mustafa, Jamal S ; Zeldin, Darryl C ; Ledent, Catherine ; Falck, John R ; Nayeem, Mohammed A |
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Zeitschrift: | The FASEB Journal ; volume 27, issue S1 ; ISSN 0892-6638 1530-6860, 2013 |
Veröffentlichung: | Wiley, 2013 |
Medientyp: | academicJournal |
DOI: | 10.1096/fasebj.27.1_supplement.1092.4 |
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