Epoxyeicosatrienoic acids mediate adenosine-induced vasodilation in rat preglomerular microvessels (PGMV) via A 2A receptors

M. K. Cheng, A. B. Doumad, H. Jiang, J R Falck, J. C. McGiff, M. A. Carroll

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


1. Activation of rat adenosine 2A receptors (A 2A R) dilates preglomerular microvessels (PGMV), an effect mediated by epoxyeicosatrienoic acids (EETs). 2. Incubation of PGMV with a selective A 2A R agonist, 2-p-(2-carboxyethyl) phenethylamino-5′-N- ethylcarboxamidoadenosine (CGS 21680; 100 μM), increased isolated PGMV EET levels to 7.57±1.53 ng mg -1 protein from 1.06±0.22 ng mg -1 protein in controls (P<0.05), without affecting hydroxyeicosatetraenoic acid (HETE) levels (10.8±0.69 vs 11.02±0.74 ng mg -1 protein). 3. CGS 21680-stimulated EETs was abolished by preincubation with an A 2A R antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol (ZM241385) (100 μM). A selective epoxygenase inhibitor, methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH; 12 μM) prevented CGS 21680-induced increase in EETs, indicating inhibition of de novo synthesis of EETs. 4. In pressurized (80 mmHg) renal arcuate arteries (110-130 μm) preconstricted with phenylephrine (20 nM), superfusion with CGS 21680 (0.01-10 μM) increased the internal diameter (i.d.) concentration-dependently; vasodilation was independent of nitric oxide and cyclooxygenase activity. CGS 21680 (10 μM) increased i.d. by 32±6 μm; vasodilation was prevented by inhibition of EET synthesis with MS-PPOH. 5. Addition of 3nM 5,6-EET, 8,9-EET and 11,12-EET increased i.d. by 53±9, 17±4 and 53±5 μm, respectively, whereas 14,15-EET was inactive. The responses to 5,6-EET were, however, significantly inhibited by indomethacin. 6. We conclude that 11,12-EET is the likely mediator of A 2A R-induced dilation of rat PGMV. Activation of A 2A R coupled to de novo EET stimulation may represent an important mechanism in regulating preglomerular microvascular tone.

Original languageEnglish (US)
Pages (from-to)441-448
Number of pages8
JournalBritish Journal of Pharmacology
Issue number3
StatePublished - Feb 2004


  • A receptors
  • A receptors
  • Adenosine
  • Cytochrome P450
  • Rat renal artery
  • Renal EETs

ASJC Scopus subject areas

  • Pharmacology


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