Department of Biomedical Sciences, Physiology of Circulation, Kidney and Lung, University of Copenhagen, Copenhagen, Denmark.
Trelleborg Hospital, Trelleborg, Sweden.
Exp Physiol. 2024 May;109(5):791-803. doi: 10.1113/EP091618. Epub 2024 Mar 9.
The mechanisms behind renal vasodilatation elicited by stimulation of β-adrenergic receptors are not clarified. As several classes of K channels are potentially activated, we tested the hypothesis that KV7 and BKCa channels contribute to the decreased renal vascular tone in vivo and in vitro. Changes in renal blood flow (RBF) during β-adrenergic stimulation were measured in anaesthetized rats using an ultrasonic flow probe. The isometric tension of segmental arteries from normo- and hypertensive rats and segmental arteries from wild-type mice and mice lacking functional K7.1 channels was examined in a wire-myograph. The β-adrenergic agonist isoprenaline increased RBF significantly in vivo. Neither activation nor inhibition of K7 and BK channels affected the β-adrenergic RBF response. In segmental arteries from normo- and hypertensive rats, inhibition of K7 channels significantly decreased the β-adrenergic vasorelaxation. However, inhibiting BK channels was equally effective in reducing the β-adrenergic vasorelaxation. The β-adrenergic vasorelaxation was not different between segmental arteries from wild-type mice and mice lacking K7.1 channels. As opposed to rats, inhibition of K7 channels did not affect the murine β-adrenergic vasorelaxation. Although inhibition and activation of K7 channels or BK channels significantly changed baseline RBF in vivo, none of the treatments affected β-adrenergic vasodilatation. In isolated segmental arteries, however, inhibition of K7 and BK channels significantly reduced the β-adrenergic vasorelaxation, indicating that the regulation of RBF in vivo is driven by several actors in order to maintain an adequate RBF. Our data illustrates the challenge in extrapolating results from in vitro to in vivo conditions.
β-肾上腺素受体刺激引起的肾血管舒张的机制尚不清楚。由于有几类 K 通道可能被激活，我们假设 KV7 和 BKCa 通道有助于体内和体外降低肾血管张力。在麻醉大鼠中，使用超声流量探头测量β-肾上腺素刺激期间的肾血流量（RBF）变化。在wire-myograph 中检查了来自正常血压和高血压大鼠的节段动脉以及来自缺乏功能性 K7.1 通道的野生型小鼠和小鼠的节段动脉的等长张力。β-肾上腺素激动剂异丙肾上腺素显著增加了体内的 RBF。K7 和 BK 通道的激活或抑制均不影响β-肾上腺素的 RBF 反应。在来自正常血压和高血压大鼠的节段动脉中，抑制 K7 通道显著降低了β-肾上腺素的血管舒张作用。然而，抑制 BK 通道同样有效地减少了β-肾上腺素的血管舒张作用。来自野生型小鼠和缺乏 K7.1 通道的小鼠的节段动脉之间的β-肾上腺素血管舒张作用没有差异。与大鼠不同，抑制 K7 通道不会影响小鼠的β-肾上腺素血管舒张作用。尽管抑制和激活 K7 通道或 BK 通道显著改变了体内的基础 RBF，但没有一种治疗方法影响β-肾上腺素的血管舒张作用。然而，在分离的节段动脉中，抑制 K7 和 BK 通道显著降低了β-肾上腺素的血管舒张作用，这表明体内 RBF 的调节由几个因素驱动，以维持足够的 RBF。我们的数据说明了将体外结果推断到体内条件的挑战。
