TY - JOUR

T1 - The renal vasodilatation from β-adrenergic activation in vivo in rats is not driven by KV7 and BKCa channels.

AU - Sorensen, Charlotte Mehlin

AU - Salomonsson, Max

AU - Lubberding, Anniek Frederike

AU - Holstein-Rathlou, Niels-Henrik

N1 - © 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

PY - 2024/3/9

Y1 - 2024/3/9

N2 - 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 K V 7.1 channels was examined in a wire-myograph. The β-adrenergic agonist isoprenaline increased RBF significantly in vivo. Neither activation nor inhibition of K V 7 and BK Ca channels affected the β-adrenergic RBF response. In segmental arteries from normo- and hypertensive rats, inhibition of K V 7 channels significantly decreased the β-adrenergic vasorelaxation. However, inhibiting BK Ca 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 K V 7.1 channels. As opposed to rats, inhibition of K V 7 channels did not affect the murine β-adrenergic vasorelaxation. Although inhibition and activation of K V 7 channels or BK Ca channels significantly changed baseline RBF in vivo, none of the treatments affected β-adrenergic vasodilatation. In isolated segmental arteries, however, inhibition of K V 7 and BK Ca 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.

AB - 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 K V 7.1 channels was examined in a wire-myograph. The β-adrenergic agonist isoprenaline increased RBF significantly in vivo. Neither activation nor inhibition of K V 7 and BK Ca channels affected the β-adrenergic RBF response. In segmental arteries from normo- and hypertensive rats, inhibition of K V 7 channels significantly decreased the β-adrenergic vasorelaxation. However, inhibiting BK Ca 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 K V 7.1 channels. As opposed to rats, inhibition of K V 7 channels did not affect the murine β-adrenergic vasorelaxation. Although inhibition and activation of K V 7 channels or BK Ca channels significantly changed baseline RBF in vivo, none of the treatments affected β-adrenergic vasodilatation. In isolated segmental arteries, however, inhibition of K V 7 and BK Ca 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.

U2 - 10.1113/EP091618

DO - 10.1113/EP091618

M3 - Journal article

C2 - 38460127

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

ER -