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K7.1 通道阻断抑制动脉血压阶跃下降触发的新生儿肾自身调节。

K7.1 channel blockade inhibits neonatal renal autoregulation triggered by a step decrease in arterial pressure.

机构信息

Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee.

School of Health Studies, University of Memphis, Memphis, Tennessee.

出版信息

Am J Physiol Renal Physiol. 2022 Feb 1;322(2):F197-F207. doi: 10.1152/ajprenal.00568.2020. Epub 2022 Jan 10.

Abstract

K7 channels, the voltage-gated K channels encoded by KCNQ genes, mediate heterogeneous vascular responses in rodents. Postnatal changes in the functional expression of K7 channels have been reported in rodent saphenous arteries, but their physiological function in the neonatal renal vascular bed is unclear. Here, we report that, unlike adult pigs, only KCNQ1 (K7.1) out of the five members of KCNQ genes was detected in neonatal pig renal microvessels. KCNQ1 is present in fetal pig kidneys as early as of gestation, and the level of expression remains the same up to . Activation of renal vascular smooth muscle cell (SMC) K7.1 stimulated whole cell currents, inhibited by HMR1556 (HMR), a selective K7.1 blocker. HMR did not change the steady-state diameter of isolated renal microvessels. Similarly, intrarenal artery infusion of HMR did not alter mean arterial pressure, renal blood flow, and renal vascular resistance in the pigs. An ∼20 mmHg reduction in mean arterial pressure evoked effective autoregulation of renal blood flow, which HMR inhibited. We conclude that ) the expression of KCNQ isoforms in porcine renal microvessels is dependent on kidney maturation, ) K7.1 is functionally expressed in neonatal pig renal vascular SMCs, ) a decrease in arterial pressure up to 20 mmHg induces renal autoregulation in neonatal pigs, and ) SMC K7.1 does not control basal renal vascular tone but contributes to neonatal renal autoregulation triggered by a step decrease in arterial pressure. K7.1 is present in fetal pig kidneys as early as of gestation, and the level of expression remains the same up to . K7.1 is functionally expressed in neonatal pig renal vascular smooth muscle cells (SMCs). A decrease in arterial pressure up to 20 mmHg induces renal autoregulation in neonatal pigs. Although SMC K7.1 does not control basal renal vascular resistance, its inhibition blunts neonatal renal autoregulation engendered by a step decrease in arterial pressure.

摘要

K7 通道是由 KCNQ 基因编码的电压门控 K 通道,介导啮齿动物血管的异质性反应。已有报道称,在啮齿动物隐静脉中,K7 通道的功能表达在出生后发生变化,但它们在新生肾血管床中的生理功能尚不清楚。在这里,我们报告称,与成年猪不同,只有 KCNQ1(K7.1)在新生猪肾微血管中被检测到,而这五个 KCNQ 基因的成员。KCNQ1 早在妊娠 115 天时就存在于胎猪肾脏中,其表达水平一直保持到 135 天。激活肾血管平滑肌细胞(SMC)K7.1 可刺激全细胞电流,被选择性 K7.1 阻断剂 HMR1556(HMR)抑制。HMR 并未改变分离的肾微血管的稳态直径。同样,肾内动脉内输注 HMR 也没有改变猪的平均动脉压、肾血流量和肾血管阻力。平均动脉压降低约 20mmHg 可诱发肾血流量的有效自身调节,而 HMR 抑制了这种自身调节。我们得出结论:)猪肾微血管中 KCNQ 同工型的表达依赖于肾脏成熟,)K7.1 在新生猪肾血管平滑肌细胞中功能性表达,)动脉压降低 20mmHg 可诱导新生猪的肾自身调节,)SMC K7.1 不控制基础肾血管张力,但有助于由动脉压阶跃降低触发的新生肾自身调节。KCNQ1 早在妊娠 115 天时就存在于胎猪肾脏中,其表达水平一直保持到 135 天。K7.1 在新生猪肾血管平滑肌细胞(SMC)中功能性表达。动脉压降低 20mmHg 可诱导新生猪的肾自身调节。尽管 SMC K7.1 不控制基础肾血管阻力,但它的抑制会削弱由动脉压阶跃降低引起的新生肾自身调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a420/8816635/c9b0849f45f1/f-00568-2020r01.jpg

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