内过氧化物 4 或血栓素 A 受体阻断对心力衰竭大鼠静态机械反射激活无影响。
No effect of endoperoxide 4 or thromboxane A receptor blockade on static mechanoreflex activation in rats with heart failure.
机构信息
Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA.
出版信息
Exp Physiol. 2020 Nov;105(11):1840-1854. doi: 10.1113/EP088835. Epub 2020 Oct 6.
NEW FINDINGS
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.
ABSTRACT
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.
新发现
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。
摘要
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。
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