Attenuation of autonomic reflexes by A803467 may not be solely caused by blockade of NaV 1.8 channels

Abstract

In decerebrated rats, we determined the dose of A803467, a NaV 1.8 antagonist, needed to attenuate the reflex pressor responses to femoral arterial injections of lactic acid (24mM; ~0.1ml) and capsaicin (0.1μg), agents which stimulate thin fiber afferents having NaV 1.8 channels. We also determined whether the dose of A803467 needed to attenuate these reflex responses affected the responses of muscle spindle afferents to tendon stretch and succinylcholine (200μg). Spindle afferents are not supplied with NaV 1.8 channels, and consequently their responses to these stimuli should not be influenced by A803467. Pressor responses to lactic acid and capsaicin were not altered by 500μg of A803467 (n=6). A803467 in a dose of 1mg, however, significantly reduced (p<0.05; n=12) the pressor responses to lactic acid (23±5 to 7±3ΔmmHg) and capsaicin (47±5 to 31±5ΔmmHg). Surprisingly, we also found that 1mg of A803467 reduced the responses of 10 spindle afferents to succinylcholine (34±11 to 4±3Δimp/s; p<0.05) and stretch (83±17 to 0.4±1Δimp/s; p<0.05). We conclude that A803467 reduces the reflex response to lactic acid and capsaicin; however, it may be working on multiple channels, including NaV 1.8, other NaVs as well as voltage-gated calcium channels.