KV7.1 channel blockade inhibits neonatal renal autoregulation triggered by a step decrease in arterial pressure.

KV7.1 channel blockade inhibits neonatal renal autoregulation triggered by a step decrease in arterial pressure.
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KV7.1 通道阻断可抑制由动脉压逐步降低引发的新生儿肾脏自动调节。

DOI:
10.1152/ajprenal.00568.2020
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发表时间:
2022
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Adebiyi,Adebowale
Adebiyi,Adebowale
中科院分区:
--
文献类型:
--
作者:
Peixoto-Neves,Dieniffer;Kanthakumar,Praghalathan;Afolabi,JeremiahM;Soni,Hitesh;Buddington,RandalK;Adebiyi,Adebowale

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KV7通道是由KCNQ基因编码的电压门控性钾离子通道,介导啮齿类动物的异质性血管反应。KV7通道的功能表达在啮齿动物隐动脉中的出生后变化已有报道,但其在新生儿肾血管床中的生理功能尚不清楚。在这里,我们报告说,与成年猪,只有KCNQ 1(KV7.1)的KCNQ基因的五个成员中检测到新生猪肾微血管。KCNQ1在妊娠50d时就已存在于胎猪肾脏中,其表达水平一直保持到出生后21天。肾血管平滑肌细胞(SMC)KV7.1的激活可刺激全细胞电流,可被选择性KV7.1阻断剂HMR 1556(HMR)抑制。HMR不改变离体肾微血管的稳态直径。同样,肾动脉内输注HMR不会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20 mmHg可引起肾血流量的有效自动调节,而HMR可抑制这种自动调节。我们的结论是:1)KCNQ亚型在猪肾微血管中的表达依赖于肾脏的成熟,2)KV 7.1在新生猪肾血管SMC中功能性表达,3)动脉压降低至20 mmHg诱导新生猪肾自动调节,和4)SMC KV7.1不控制基础肾血管张力,但有助于由动脉压逐步降低触发的新生儿肾自动调节。NOTEWORTHYKV7.1早在妊娠50天就存在于胎猪肾脏中,并且表达水平保持不变直到出生后21天。KV7.1在新生猪肾血管平滑肌细胞(SMC)中功能性表达。动脉压降低至20 mmHg可诱导新生猪的肾脏自动调节。虽然SMC KV7.1不控制基础肾血管阻力,但其抑制作用减弱了由动脉压逐步降低引起的新生儿肾自动调节。
KV7 channels, the voltage-gated K+channels encoded by KCNQ genes, mediate heterogeneous vascular responses in rodents. Postnatal changes in the functional expression of KV7 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 (KV7.1) out of the five members of KCNQ genes was detected in neonatal pig renal microvessels. KCNQ1 is present in fetal pig kidneys as early asday 50of gestation, and the level of expression remains the same up topostnatal day 21. Activation of renal vascular smooth muscle cell (SMC) KV7.1 stimulated whole cell currents, inhibited by HMR1556 (HMR), a selective KV7.1 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 that1) the expression of KCNQ isoforms in porcine renal microvessels is dependent on kidney maturation,2) KV7.1 is functionally expressed in neonatal pig renal vascular SMCs,3) a decrease in arterial pressure up to 20 mmHg induces renal autoregulation in neonatal pigs, and4) SMC KV7.1 does not control basal renal vascular tone but contributes to neonatal renal autoregulation triggered by a step decrease in arterial pressure.NEW & NOTEWORTHYKV7.1 is present in fetal pig kidneys as early asday 50of gestation, and the level of expression remains the same up topostnatal day 21. KV7.1 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 KV7.1 does not control basal renal vascular resistance, its inhibition blunts neonatal renal autoregulation engendered by a step decrease in arterial pressure.
DOI: 10.1016/s0021-9258(19)68921-0
发表时间: 1981-08
期刊: The Journal of biological chemistry
影响因子: --
作者:
K. McEntee;G. Weinstock;I. Lehman
通讯作者: K. McEntee;G. Weinstock;I. Lehman
DOI: --
发表时间: 1985
期刊: The Journal of biological chemistry
影响因子: --
作者:
Riddles,PW;Lehman,IR
通讯作者: Lehman,IR
DOI: --
发表时间: 1981
期刊: The Journal of biological chemistry
影响因子: --
作者:
Weinstock,GM;McEntee,K;Lehman,IR
通讯作者: Lehman,IR
DOI: 10.1016/0092-8674(82)90054-x
发表时间: 1982-01-01
期刊: CELL
影响因子: 64.5
作者:
FLORY, J;RADDING, CM
通讯作者: RADDING, CM
DOI: 10.1073/pnas.76.4.1702
发表时间: 1979-01-01
影响因子: 11.1
作者:
MEYER, RR;GLASSBERG, J;KORNBERG, A
通讯作者: KORNBERG, A