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EXAMINATION OF ADENOSINE RECEPTOR‐MEDIATED RELAXATION OF THE PIG CORONARY ARTERY
Author(s) -
Lew Michael J,
Kao Sheau W
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03054.x
Subject(s) - adenosine , adenosine receptor , cardiology , medicine , receptor , artery , adenosine a1 receptor , chemistry , endocrinology , agonist
1. The adenosine receptors mediating relaxation of porcine isolated left anterior descending coronary arteries (LAD) and the effects of the level and type of preconstriction on the responses to adenosine analogues were examined in the present study. 2. Relaxation responses to the non‐selective adenosine receptor agonist N ‐ethylcarboxamidoadenosine (NECA) were endothelium independent. N ‐Ethylcarboxamidoadenosine, GR 79236 (A 1 receptor selective) and 8‐cyclopentyl‐1,3‐dipropylxanthine (CGS 21680) (A 2A receptor selective) produced full relaxation in LAD precontracted to 50% of the response to potassium depolarization with the thromboxane receptor agonist U46619. The order of potency was CGS 21680 = NECA > GR 79236, consistent with that defining the A 2A receptor subtype. 3. 3,7‐Dimethyl‐1‐propargylxanthine (DMPX; A 2 receptor selective) competitively antagonized NECA and CGS 21680 with pK B values of 4.95±0.09 and 5.06±0.22, respectively. The A 1 receptor selective antagonist 1,3‐[ 3 H]‐dipropyl‐8‐cyclopentylxanthine (DPCPX) had no effect on NECA relaxation, even in the presence of DMPX. 4. The sensitivity to relaxation by NECA was dependent on the precontracting agent. Arteries precontracted with endothelin (ET)‐1 were most sensitive to NECA, U46619‐precontracted arteries were intermediate and KCl‐precontracted arteries were least sensitive. 5. The potency of NECA was reduced when the preconstriction level was increased from 50 to 90% of maximum in U46619‐precontracted arteries (pEC 50 7.94±0.12 and 7.35±0.04, respectively) and, in KCl‐precontracted arteries, both the potency and maximum effect of NECA were reduced when the preconstriction level increased from 50 to 80% of maximum (pEC 50 7.52±0.13 and 6.91±0.26, respectively; maximum responses 82.5±10.2 and 23.9±3.6%, respectively, of the preconstricted tone). Relaxation responses to NECA were independent of the level of precontraction in ET‐1‐precontracted arteries. 6. In porcine LAD, relaxation responses to adenosine analogues were endothelium independent and were mediated via A 2A adenosine receptors. Responses to NECA were dependent on both the level and type of preconstriction.