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Adenosine receptor subtypes and vasodilatation in rat skeletal muscle during systemic hypoxia: a role for A 1 receptors
Author(s) -
Bryan Philip T.,
Marshall Janice M.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.151af.x
Subject(s) - adenosine , medicine , endocrinology , adenosine receptor , agonist , adenosine a2a receptor , cgs 21680 , ccpa , adenosine a1 receptor , hypoxia (environmental) , anesthesia , chemistry , receptor , oxygen , organic chemistry
1 In anaesthetized rats we tested responses evoked by systemic hypoxia (breathing 8% O 2 for 5 min) and adenosine (i.a. infusion for 5 min) before and after administration of a selective adenosine A 1 receptor antagonist DPCPX (8‐cyclopentyl‐1,3‐dipropylxanthine), or a selective adenosine A 2A receptor antagonist ZM 241385. Arterial blood pressure, (ABP), heart rate (HR), femoral blood flow (FBF) and femoral vascular conductance (FVC: FBF/ABP) were recorded together with the K + concentration in arterial blood ([K + ] a ) and in venous blood of hindlimb muscle ([K + ] v ) before and at the 5th minute of hypoxia or agonist infusion. 2 In 12 rats, DPCPX reversed the fall in ABP and HR and the increase in FVC evoked by the selective A 1 agonist CCPA (2‐chloro‐ N 6 ‐cyclopentyladenosine; i.a. infusion for 5 min). DPCPX also reduced both the increase in FVC induced by hypoxia and that induced by adenosine; the control responses to these stimuli were comparable in magnitude and both were reduced by ∼50%. 3 In 11 rats, ZM 241385 reversed the fall in ABP and increase in FVC evoked by the selective A 2A agonist CGS 21680 (2‐ p ‐(2‐carboxyethyl)‐phenethylamino‐5′‐ N ‐ethylcarboxamidoadenosine hydrochloride; i.a. infusion for 5 min). ZM 241385 also reduced the increase in FVC induced by adenosine by ∼50%, but had no effect on the increase in FVC induced by hypoxia. 4 In these same studies, before administration of DPCPX, or ZM 241385, hypoxia had no effect on the venous‐arterial difference for K + ([K + ] v‐a ), whereas after administration of either antagonist, hypoxia significantly reduced [K + ] v‐a suggesting an increase in hypoxia‐induced K + uptake, or a reduction in K + efflux. 5 These results indicate that both A 1 and A 2A receptors are present in hindlimb muscle and can mediate vasodilatation and that A 1 and A 2A receptors contribute equally to dilatation induced by infused adenosine. However, they suggest that endogenous adenosine released during systemic hypoxia induces dilatation only by acting on A 1 receptors. Given previous evidence that adenosine can stimulate receptors on skeletal muscle fibres that are coupled to ATP‐sensitive K + (K ATP ) channels so promoting K + efflux, our results allow the proposal that K ATP channels may be coupled to both A 1 and to A 2A receptors and may be stimulated to open by adenosine released during hypoxia, but indicate that, during systemic hypoxia, K + efflux caused by either receptor subtype makes a very minor contribution to the muscle vasodilatation.