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Epoxyeicosatrienoic acids mediate adenosine‐induced vasodilation in rat preglomerular microvessels (PGMV) via A 2A receptors
Author(s) -
Cheng M K,
Doumad A B,
Jiang H,
Falck J R,
McGiff J C,
Carroll M A
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705640
Subject(s) - epoxygenase , vasodilation , adenosine , cgs 21680 , endocrinology , medicine , chemistry , agonist , phenylephrine , adenosine receptor , antagonist , cyclooxygenase , receptor , arachidonic acid , biochemistry , biology , enzyme , blood pressure
Activation of rat adenosine 2A receptors (A 2A R) dilates preglomerular microvessels (PGMV), an effect mediated by epoxyeicosatrienoic acids (EETs). Incubation of PGMV with a selective A 2A R agonist, 2‐ p ‐(2‐carboxyethyl) phenethylamino‐5′‐ N ‐ethylcarboxamidoadenosine (CGS 21680; 100 μ M ), 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). 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 μ M ). A selective epoxygenase inhibitor, methylsulfonyl‐propargyloxyphenylhexanamide (MS‐PPOH; 12 μ M ) prevented CGS 21680‐induced increase in EETs, indicating inhibition of de novo synthesis of EETs. In pressurized (80 mmHg) renal arcuate arteries (110–130 μ m) preconstricted with phenylephrine (20 n M ), superfusion with CGS 21680 (0.01–10 μ M ) increased the internal diameter (i.d.) concentration‐dependently; vasodilation was independent of nitric oxide and cyclooxygenase activity. CGS 21680 (10 μ M ) increased i.d. by 32±6 μ m; vasodilation was prevented by inhibition of EET synthesis with MS‐PPOH. Addition of 3 n M 5,6‐EET, 8,9‐EET and 11,12‐EET increased i.d. by 53±9, 17±4 and 53±5 μ m, respectively, whereas 14,15‐EET was inactive. The responses to 5,6‐EET were, however, significantly inhibited by indomethacin. 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.British Journal of Pharmacology (2004) 141 , 441–448. doi: 10.1038/sj.bjp.0705640