Sex-dependent attenuating effects of capsaicin administration on the mechanoreflex in healthy rats.
Sex-dependent attenuating effects of capsaicin administration on the mechanoreflex in healthy rats.
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辣椒素给药对健康大鼠机械感受反射的性别依赖性减弱作用。
DOI：
10.1152/ajpheart.00237.2023
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Copp,StevenW
中科院分区：
文献类型：
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作者：
Butenas,AlecLE;Ishizawa,Rie;Rollins,KorynneS;Mizuno,Masaki;Copp,StevenW
对第 III 组和第 IV 组细纤维肌肉传入感觉末梢上的机械敏感通道的刺激会激活机械感受反射，这有助于运动期间交感神经活动 (SNA) 和血压的反射增加。越来越多的证据表明，用辣椒素激活细纤维传入感觉末梢上的非选择性阳离子通道瞬时受体电位 vanilloid-1 (TRPV1) 可能会减弱机械感觉。然而，没有研究调查辣椒素对机械感受反射的影响。我们测试了这样的假设：在雄性和雌性去大脑、未麻醉的大鼠中，将辣椒素 (0.05 µg) 注射到后肢的动脉供应中，会降低对 30 秒 1 Hz 节律性后肢肌肉拉伸（孤立的机械感受反射激活模型）的升压和肾 SNA (RSNA) 反应。在雄性大鼠（n=8）中，注射辣椒素显着降低了综合血压（血压指数或 BPI：术前，363±±78；术后，211±±88 mmHg·s；P= 0.023）和 RSNA [∫ΔRSNA；前，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（n=8）中，注射辣椒素对升压（BPI；前：277 ± 67；后：207 ± 77 mmHg·s；P= 0.343）或RSNA（∫ΔRSNA：前，697 ± 123；后，440 ± 183）没有显着影响。 au;P= 0.307) 对后肢肌肉拉伸的反应。数据表明，将辣椒素注射到后肢动脉供应中以刺激细纤维肌肉传入感觉末梢上的 TRPV1 会减弱健康雄性大鼠的机械感受反射，但不会减弱雌性大鼠的机械感受反射。这些发现可能对慢性疾病具有重要意义，在慢性疾病中，过度的机械感受性反射会导致运动期间交感神经兴奋异常。新的和值得注意的最近在孤立的感觉神经元中的证据表明，辣椒素诱导的 TRPV1 刺激会减弱机械敏感性。在这里，我们首次证明，辣椒素暴露/施用会降低雄性大鼠体内的反射升压和肾交感神经对机械感受反射激活的反应，但不会降低雌性大鼠体内的反应。我们的数据可能对慢性疾病具有重要的临床意义，这些慢性疾病与过度的机械感受反射有关，至少在男性中是如此。
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 (n= 8), capsaicin injection significantly reduced the integrated blood pressure (blood pressure index or BPI: pre, 363 ± 78; post, 211 ± 88 mmHg·s;P= 0.023) and RSNA [∫ΔRSNA; pre, 687 ± 206; post, 216 ± 80 arbitrary units (au),P= 0.049] response to hindlimb muscle stretch. In female rats (n= 8), capsaicin injection had no significant effect on the pressor (BPI; pre: 277 ± 67; post: 207 ± 77 mmHg·s;P= 0.343) or RSNA (∫ΔRSNA: pre, 697 ± 123; post, 440 ± 183 au;P= 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.NEW & NOTEWORTHYRecent 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.