Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA.
Exp Physiol. 2020 Nov;105(11):1840-1854. doi: 10.1113/EP088835. Epub 2020 Oct 6.
What is the central question of this study? Do endoperoxide 4 and thromboxane A receptors, which are receptors for cyclooxygenase products of arachidonic metabolism, on thin fibre muscle afferents play a role in the chronic mechanoreflex sensitization present in rats with heart failure with reduced ejection fraction (HF-rEF)? What is the main finding and its importance? The data do not support a role for endoperoxide 4 receptors or thromboxane A receptors in the chronic mechanoreflex sensitization in HF-rEF rats.
We investigated the role of cyclooxygenase metabolite-associated endoperoxide 4 receptors (EP4-R) and thromboxane A receptors (TxA -R) on thin fibre muscle afferents in the chronic mechanoreflex sensitization in rats with myocardial infarction-induced heart failure with reduced ejection fraction (HF-rEF). We hypothesized that injection of either the EP4-R antagonist L-161,982 (1 µg) or the TxA -R antagonist daltroban (80 µg) into the arterial supply of the hindlimb would reduce the increase in blood pressure and renal sympathetic nerve activity (RSNA) evoked in response to 30 s of static hindlimb skeletal muscle stretch (a model of isolated mechanoreflex activation) in decerebrate, unanaesthetized HF-rEF rats but not sham-operated control rats (SHAM). Ejection fraction was significantly reduced in HF-rEF (45 ± 11%) compared to SHAM (83 ± 6%; P < 0.01) rats. In SHAM and HF-rEF rats, we found that the EP4-R antagonist had no effect on the peak increase in mean arterial pressure (peak ΔMAP SHAM n = 6, pre: 15 ± 7, post: 15 ± 9, P = 0.99; HF-rEF n = 9, pre: 30 ± 11, post: 32 ± 15 mmHg, P = 0.84) or peak increase in RSNA (peak ΔRSNA SHAM pre: 33 ± 14, post: 47 ± 31%, P = 0.94; HF-rEF, pre: 109 ± 47, post: 139 ± 150%, P = 0.76) response to stretch. Similarly, in SHAM and HF-rEF rats, we found that the TxA -R antagonist had no effect on the peak ΔMAP (SHAM n = 7, pre: 13 ± 7, post: 19 ± 14, P = 0.15; HF-rEF n = 14, pre: 24 ± 13, post: 21 ± 13 mmHg, P = 0.47) or peak ΔRSNA (SHAM pre: 52 ± 43, post: 57 ± 67%, P = 0.94; HF-rEF, pre: 108 ± 93, post: 88 ± 72%, P = 0.30) response to stretch. The data do not support a role for EP4-Rs or TxA -Rs in the chronic mechanoreflex sensitization in HF-rEF.
本研究的核心问题是什么？环氧合酶产物前列腺素内过氧化物 4 和血栓素 A 受体（花生四烯酸代谢的环氧化酶产物的受体）在薄纤维肌传入纤维上是否在射血分数降低的心力衰竭（HF-rEF）大鼠中存在的慢性机械反射敏感化中发挥作用？主要发现及其重要性是什么？数据不支持环氧合酶代谢产物相关的内过氧化物 4 受体（EP4-R）或血栓素 A 受体（TxA-R）在 HF-rEF 大鼠的慢性机械反射敏感化中发挥作用。
我们研究了环氧合酶代谢物相关的内过氧化物 4 受体（EP4-R）和血栓素 A 受体（TxA-R）在心肌梗死诱导的射血分数降低的心力衰竭（HF-rEF）大鼠中薄纤维肌传入纤维上的慢性机械反射敏感化中的作用。我们假设，将 EP4-R 拮抗剂 L-161,982（1µg）或 TxA-R 拮抗剂 daltroban（80µg）注入后肢动脉供应中，会降低去大脑、未麻醉的 HF-rEF 大鼠中 30 秒静态后肢骨骼肌拉伸（孤立机械反射激活的模型）引起的血压和肾交感神经活动（RSNA）的增加，但不会降低假手术对照（SHAM）大鼠的血压和 RSNA 的增加。HF-rEF 大鼠的射血分数明显降低（45±11%）与 SHAM 大鼠（83±6%；P<0.01）相比。在 SHAM 和 HF-rEF 大鼠中，我们发现 EP4-R 拮抗剂对平均动脉压的峰值增加没有影响（SHAM n=6，峰值ΔMAP SHAM 预：15±7，后：15±9，P=0.99；HF-rEF n=9，预：30±11，后：32±15mmHg，P=0.84）或 RSNA 的峰值增加（SHAM 预：33±14，后：47±31%，P=0.94；HF-rEF，预：109±47，后：139±150%，P=0.76）对拉伸的反应。同样，在 SHAM 和 HF-rEF 大鼠中，我们发现 TxA-R 拮抗剂对平均动脉压的峰值ΔMAP 没有影响（SHAM n=7，预：13±7，后：19±14，P=0.15；HF-rEF n=14，预：24±13，后：21±13mmHg，P=0.47）或 RSNA 的峰值ΔMAP（SHAM 预：52±43，后：57±67%，P=0.94；HF-rEF，预：108±93，后：88±72%，P=0.30）对拉伸的反应。数据不支持 EP4-Rs 或 TxA-Rs 在 HF-rEF 大鼠慢性机械反射敏感化中的作用。
