Department of Kinesiology, Kansas State University, Manhattan, Kansas, United States.
Department of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
Am J Physiol Heart Circ Physiol. 2023 Aug 1;325(2):H372-H384. doi: 10.1152/ajpheart.00237.2023. Epub 2023 Jun 30.
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.
刺激 III 组和 IV 组细纤维肌传入感觉末梢的机械敏感通道可激活机械反射，这有助于在运动过程中反射性增加交感神经活动（SNA）和血压。越来越多的证据表明，用辣椒素激活细纤维传入感觉末梢的非选择性阳离子通道瞬时受体电位香草素 1（TRPV1）可能会减轻机械感觉。然而，尚无研究探讨辣椒素对机械反射的影响。我们假设，在去大脑、未麻醉的雄性和雌性大鼠中，将辣椒素（0.05μg）注入后肢动脉供应中，可降低 30 秒 1Hz 节律性后肢肌肉拉伸（孤立机械反射激活模型）引起的升压和肾 SNA（RSNA）反应。在雄性大鼠中（n=8），辣椒素注射显著降低了整合血压（血压指数或 BPI：预，363±78；后，211±88mmHg·s；P=0.023）和 RSNA[∫ΔRSNA；预，687±206；后，216±80 任意单位（au）；P=0.049]对后肢肌肉拉伸的反应。在雌性大鼠中（n=8），辣椒素注射对血压（BPI；预：277±67；后：207±77mmHg·s；P=0.343）或 RSNA（∫ΔRSNA：预，697±123；后，440±183 au；P=0.307）对后肢肌肉拉伸的反应均无显著影响。数据表明，向后肢动脉供应中注射辣椒素以刺激细纤维肌传入感觉末梢上的 TRPV1 可减弱健康雄性大鼠而非雌性大鼠的机械反射。这一发现可能对慢性疾病具有重要意义，在这些疾病中，机械反射过度会导致运动期间交感神经兴奋异常。最近在分离的感觉神经元中的证据表明，辣椒素诱导的 TRPV1 刺激可减轻机械敏感性。在这里，我们首次证明，在体内，辣椒素暴露/给药可降低雄性大鼠机械反射激活时的反射性升压和肾交感神经反应，但对雌性大鼠则没有。我们的数据对于与机械反射过度相关的慢性疾病至少在男性中可能具有重要的临床意义。
