Elucidation in the rat of the role of adenosine and A2A-receptors in the hyperaemia of twitch and tetanic contractions.

Adenosine is implicated in playing a role in blood flow responses to situations where O(2) delivery is reduced (hypoxia) or O(2) consumption is increased (exercise). Strong isometric contractions have been shown to limit vasodilatation, potentially leading to a greater mismatch between and than during twitch contractions. Thus, we hypothesized that adenosine makes a greater contribution to the hyperaemia associated with isometric tetanic than isometric twitch contractions and aimed to elucidate the adenosine-receptor subtypes involved in the response. In four groups of anaesthetized rats, arterial blood pressure (ABP), femoral blood flow (FBF) and tension in the extensor digitorum longus muscle were recorded; isometric twitch and tetanic contractions were evoked by stimulation of the sciatic nerve for 5 min at 4 Hz and 40 Hz, respectively. Groups 1 (twitch) and 3 (tetanic) were time controls for Groups 2 and 4, which received the selective A(2A)-receptor antagonist ZM241385 before the third and 8-sulphophenyltheophylline (8-SPT; a non-selective adenosine receptor antagonist) before the fourth contraction. Time controls showed consistent tension and hyperaemic responses: twitch and tetanic contractions were associated with a 3-fold and 2.5-fold increase in femoral vascular conductance (FVC, FBF/ABP) from baseline, respectively. ZM241385 reduced these responses by 14% and as much as 25%, respectively; 8-SPT had no further effect. We propose that, while twitch contractions produce a larger hyperaemia, adenosine acting via A(2A)-receptors plays a greater role in the hyperaemia associated with tetanic contraction. These results are considered in relation to the A(1)-receptor-mediated muscle dilatation evoked by systemic hypoxia.