P2X2/3 and P2X3 receptors contribute to the metaboreceptor component of the exercise pressor reflex

The exercise pressor reflex is due to activation of thin fiber afferents within contracting muscle. These afferents are in part stimulated by ATP activation of purinergic 2X (P2X) receptors during contraction. Which of the P2X receptors contribute to the reflex is unknown; however, P2X2/3 and P2X3 receptor subtypes are good candidates because they are located on thin fiber afferents and are involved in sensory neurotransmission. To determine if P2X2/3 and P2X3 receptors evoke the metabolic component of the exercise pressor reflex, we examined the effect of two P2X2/3 and P2X3 antagonists, A-317491 (10 mg/kg) and RO-3 (10 mg/kg), on the pressor response to injections of alpha,beta-methylene ATP (alpha,beta-MeATP; 50 mu g/kg), freely perfused static contraction, contraction of the triceps surac muscles while the circulation was occluded, and postcontraction circulatory occlusion in decerebrate cats. We found that the antagonists reduced the pressor response to alpha,beta-MeATP injection (before Delta 20 +/- 3 mmHg; drug Delta 11 +/- 3 mmHg; P < 0.05), suggesting the antagonists were effective in blocking P2X2/3 and P2X3 receptors. P2X2/3 and P2X3 receptor blockade reduced the pressor response to freely perfused contraction (before Delta 33 +/- 5 mmHg; drug Delta 15 +/- 5 mmHg; P < 0.05), contraction with the circulation occluded (before Delta 52 +/- 7 mmHg; drug Delta 20 +/- 4 mmHg; P < 0.05), and during postcontraction circulatory occlusion (before Delta 15 +/- 1 mmHg; drug Delta 5 +/- 1 mmHg; P < 0.05). Our findings suggest that P2X2/3 and P2X3 receptors contribute to the metabolic component of the exercise pressor reflex in decerebrate cats.