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T型钙通道在肾自动调节中无明显作用。

No apparent role for T-type Ca²⁺ channels in renal autoregulation.

作者信息

Frandsen Rasmus Hassing, Salomonsson Max, Hansen Pernille B L, Jensen Lars J, Braunstein Thomas Hartig, Holstein-Rathlou Niels-Henrik, Sorensen Charlotte Mehlin

机构信息

Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.

出版信息

Pflugers Arch. 2016 Apr;468(4):541-50. doi: 10.1007/s00424-015-1770-9. Epub 2015 Dec 14.

Abstract

Renal autoregulation protects glomerular capillaries against increases in renal perfusion pressure (RPP). In the mesentery, both L- and T-type calcium channels are involved in autoregulation. L-type calcium channels participate in renal autoregulation, but the role of T-type channels is not fully elucidated due to lack of selective pharmacological inhibitors. The role of T- and L-type calcium channels in the response to acute increases in RPP in T-type channel knockout mice (CaV3.1) and normo- and hypertensive rats was examined. Changes in afferent arteriolar diameter in the kidneys from wild-type and CaV3.1 knockout mice were assessed. Autoregulation of renal blood flow was examined during acute increases in RPP in normo- and hypertensive rats under pharmacological blockade of T- and L-type calcium channels using mibefradil (0.1 μM) and nifedipine (1 μM). In contrast to the results from previous pharmacological studies, genetic deletion of T-type channels CaV3.1 did not affect renal autoregulation. Pharmacological blockade of T-type channels using concentrations of mibefradil which specifically blocks T-type channels also had no effect in wild-type or knockout mice. Blockade of L-type channels significantly attenuated renal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channels had no effect on changes in the renal vascular resistance after acute increases in RPP in normo- and hypertensive rats. These findings show that genetic deletion of T-type channels CaV3.1 or treatment with low concentrations of mibefradil does not affect renal autoregulation. Thus, T-type calcium channels are not involved in renal autoregulation in response to acute increases in RPP.

摘要

肾自动调节可保护肾小球毛细血管免受肾灌注压(RPP)升高的影响。在肠系膜中,L型和T型钙通道均参与自动调节。L型钙通道参与肾自动调节,但由于缺乏选择性药理抑制剂,T型通道的作用尚未完全阐明。研究了T型通道敲除小鼠(CaV3.1)以及正常和高血压大鼠中T型和L型钙通道对RPP急性升高的反应。评估了野生型和CaV3.1敲除小鼠肾脏中入球小动脉直径的变化。在使用米贝拉地尔(0.1μM)和硝苯地平(1μM)对T型和L型钙通道进行药理阻断的情况下,检测正常和高血压大鼠RPP急性升高期间的肾血流自动调节。与先前药理研究的结果相反,T型通道CaV3.1的基因缺失并未影响肾自动调节。使用特异性阻断T型通道的米贝拉地尔浓度对T型通道进行药理阻断,在野生型或敲除小鼠中也没有效果。阻断L型通道可显著减弱两种品系的肾自动调节。这些发现得到了体内研究的支持,即在正常和高血压大鼠中,阻断T型通道对RPP急性升高后肾血管阻力的变化没有影响。这些发现表明,T型通道CaV3.1的基因缺失或用低浓度米贝拉地尔治疗不会影响肾自动调节。因此,T型钙通道不参与对RPP急性升高的肾自动调节。

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