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A 2 ‐purinoceptor‐mediated relaxation in the guinea‐pig coronary vasculature: a role for nitric oxide
Author(s) -
Vials Amanda,
Burnstock Geoffrey
Publication year - 1993
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 - 10.1111/j.1476-5381.1993.tb13586.x
Subject(s) - adenosine , cgs 21680 , vasodilation , purinergic receptor , adenosine receptor , chemistry , agonist , medicine , nitric oxide , endocrinology , guinea pig , pharmacology , receptor
1 The Langendorff heart preparation was used to investigate the mechanism of action of the endothelium‐dependent vasodilatation evoked by adenosine and its analogues in the guinea‐pig coronary vasculature. 2 The relative order of potency of adenosine and its analogues in causing a reduction in perfusion pressure was d ‐5′‐(N‐ethylcarboxamide)adenosine (NECA) = 2‐[ p ‐(2‐carboxyethyl)phenylethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS 21680)> R ‐N 6 ‐(2‐phenylisopropyl)adenosine ( R ‐PIA) = adenosine = 2‐chloroadenosine (2‐CA)> S ‐N 6 ‐(2‐phenylisopropyl)adenosine ( S ‐PIA) = N 6 ‐cyclopentyl‐adenosine (CPA); thus suggesting the presence of A 2 ‐purinoceptors in this preparation. 3 8‐( p ‐Sulphophenyl)theophylline (8‐PSPT; 3 × 10 −5 m ) significantly reduced both the maximum amplitude and area of the vasodilatation produced in response to adenosine (5 × 10 −10 − 5 × 10 −8 mol) without having any effect on the response to the P 2 ‐purinoceptor agonist, 2‐methylthioATP. The relaxation induced by adenosine (5 × 10 −12 − 5 × 10 −8 mol) was unaffected by the selective A 1 ‐purinoceptor antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX; 10 −8 m ). This antagonist profile suggests that only A 2 ‐purinoceptors are present in the guinea‐pig coronary vasculature. 4 The areas of the vasodilator response to adenosine (5 × 10 −10 − 5 × 10 −7 mol), NECA (5 × 10 −12 − 5 × 10 −7 mol) and CGS 21680 (5 × 10 −12 − 5 × 10 −10 mol) were significantly reduced by N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME; 3 × 10 −5 m ). The amplitude of the responses to low concentrations of adenosine (5 × 10 −10 − 5 × 10 −9 mol), NECA (5 × 10 −11 mol) and CGS 21680 (5 × 10 −11 − 5 × 10 −9 mol) were significantly reduced by l ‐NAME (3 × 10 −5 m ). 5 l ‐Arginine (1.5 × 10 −3 m ) significantly reversed the inhibition, by l ‐NAME (3 × 10 −5 m ), of the relaxant response to adenosine (5 × 10 −8 mol), NECA (5 × 10 −9 mol) and CGS 21680 (5 × 10 −11 mol). 6 Indomethacin (10 −6 m ) did not inhibit the response to adenosine, except at low doses (5 × 10 −11 − 5 × 10 −10 mol). 7 It is concluded that in the guinea‐pig coronary vasculature, while a major part of the vasodilator action of adenosine is probably directly via A 2 ‐receptors on the smooth muscle, activation of a subpopulation of A 2 ‐purinoceptors on endothelial cells by adenosine and its analogues induces relaxation via production of nitric oxide; prostanoids appear to play a minimal role in the relaxation induced by adenosine as in most other preparations.