Sex-dependent attenuating effects of capsaicin administration on the mechanoreflex in healthy rats.

Stimulation of mechanically sensitive channels on the sensory endings of group III and IV thin fiber muscle afferents activates the mechanoreflex, which contributes to reflex increases in sympathetic nerve activity (SNA) and blood pressure during exercise. Accumulating evidence suggests that activation of the nonselective cation channel transient receptor potential vanilloid-1 (TRPV1) on the sensory endings of thin fiber afferents with capsaicin may attenuate mechanosensation. However, no study has investigated the effect of capsaicin on the mechanoreflex. We tested the hypothesis that in male and female decerebrate, unanesthetized rats, the injection of capsaicin (0.05 µg) into the arterial supply of the hindlimb reduces the pressor and renal SNA (RSNA) response to 30 s of 1 Hz rhythmic hindlimb muscle stretch (a model of isolated mechanoreflex activation). In male rats ( = 8), capsaicin injection significantly reduced the integrated blood pressure (blood pressure index or BPI: pre, 363 ± 78; post, 211 ± 88 mmHg·s; = 0.023) and RSNA [∫ΔRSNA; pre, 687 ± 206; post, 216 ± 80 arbitrary units (au), = 0.049] response to hindlimb muscle stretch. In female rats ( = 8), capsaicin injection had no significant effect on the pressor (BPI; pre: 277 ± 67; post: 207 ± 77 mmHg·s; = 0.343) or RSNA (∫ΔRSNA: pre, 697 ± 123; post, 440 ± 183 au; = 0.307) response to hindlimb muscle stretch. The data suggest that the injection of capsaicin into the hindlimb arterial supply to stimulate TRPV1 on the sensory endings of thin fiber muscle afferents attenuates the mechanoreflex in healthy male, but not female, rats. The findings may carry important implications for chronic conditions in which an exaggerated mechanoreflex contributes to aberrant sympathoexcitation during exercise. Recent evidence in isolated sensory neurons indicates that capsaicin-induced stimulation of TRPV1 attenuates mechanosensitivity. Here we demonstrate for the first time that capsaicin exposure/administration reduces the reflex pressor and renal sympathetic nerve response to mechanoreflex activation in male rats, but not female rats, in vivo. Our data may carry important clinical implications for chronic diseases which have been linked to an exaggerated mechanoreflex, at least in males.