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T-type calcium channels in the regulation of afferent and efferent arterioles in rats.

机译:T型钙通道在大鼠传入和传出小动脉的调节中。

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L-type Ca2+ channels predominantly influence preglomerular arterioles, but there is less information regarding the role of T-type Ca2+ channels in regulating the renal microvasculature. We compared the effects of T- and L-type channel blockade on afferent and efferent arterioles using the in vitro blood-perfused juxtamedullary nephron preparation. Single afferent or efferent arterioles of Sprague-Dawley rats were visualized and superfused with solutions containing Ca2+ channel blockers. We confirmed that L-type channel blockade with diltiazem dilates afferent arterioles but has no significant effects on efferent arterioles. In contrast, T-type channel blockade with pimozide (10 micromol/l) or mibefradil (1 micromol/l) dilated both afferent (26.8 +/- 3.4 and 24.6 +/- 1.9%) and efferent (19.2 +/- 2.9 and 19.1 +/- 4.8%) arterioles. Adding diltiazem did not significantly augment the dilation of afferent arterioles elicited by pimozide and mibefradil, and adding pimozide after diltiazem likewise did not elicit further vasodilation. Diltiazem blocked the depolarization-induced afferent arteriolar constriction elicited by 55 mM KCl; however, the constrictor response to KCl remained intact during treatment with 10 microM pimozide. Pimozide also prevented the afferent arterioles from exhibiting autoregulatory-mediated constrictor responses to increases in perfusion pressure. We conclude that T-type channel blockers dilate efferent arterioles as well as afferent arterioles and diminish afferent arteriolar autoregulatory responses to changes in perfusion pressure. To the extent that these agents exert their effects primarily on T-type Ca2+ channels in our experimental setting, these results indicate that T-type channels are functionally expressed in juxtamedullary afferent and efferent arterioles and may act cooperatively with L-type channels to regulate afferent arteriolar resistance. Because L-type channels are not functionally expressed in efferent arterioles, T-type channels may be particularly significant in the regulation of efferent arteriolar function.
机译:L型Ca2 +通道主要影响肾小球前小动脉,但关于T型Ca2 +通道在调节肾微血管中的作用的信息较少。我们比较了使用体外血液灌输近髓肾单位制备的T型和L型通道阻滞对传入和传出小动脉的影响。可视化Sprague-Dawley大鼠的单个传入或传出的小动脉,并与含Ca2 +通道阻滞剂的溶液相融合。我们证实,地尔硫卓的L型通道阻滞可扩张传入小动脉,但对传出小动脉没有明显影响。相比之下,吡莫司特(10 micromol / l)或咪贝拉地尔(1 micromol / l)的T型通道阻滞扩张了传入(26.8 +/- 3.4和24.6 +/- 1.9%)和传出(19.2 +/- 2.9 19.1 +/- 4.8%)的小动脉。添加地尔硫卓并没有显着增加由匹莫齐德和米贝地尔引起的传入小动脉的扩张,在地尔硫卓后添加匹莫齐德同样也没有引起进一步的血管舒张。地尔硫卓阻断了由55 mM KCl引起的去极化诱导的传入小动脉收缩。然而,在用10 microM吡美唑治疗期间,对KCl的收缩反应仍然完整。 Pimozide还可以防止传入小动脉对灌注压力的升高表现出自动调节介导的收缩反应。我们得出的结论是,T型通道阻滞剂可扩张传入小动脉以及传入小动脉,并减少对灌注压力变化的传入小动脉自调节反应。在我们的实验环境中,这些药物主要在T型Ca2 +通道上发挥作用,这些结果表明T型通道在近髓小传入和传出小动脉中功能性表达,并且可能与L型通道协同作用来调节传入小动脉阻力。由于L型通道在传出小动脉中未功能性表达,因此T型通道在传出小动脉功能的调节中可能特别重要。

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