The renal vasodilatation from -adrenergic activation in vivo in rats is not driven by K_V7 and BK_Ca channels

The mechanisms behind renal vasodilatation elicited by stimulation of beta-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 beta-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 beta-adrenergic agonist isoprenaline increased RBF significantly in vivo. Neither activation nor inhibition of K(V)7 and BKCa channels affected the beta-adrenergic RBF response. In segmental arteries from normo- and hypertensive rats, inhibition of K(V)7 channels significantly decreased the beta-adrenergic vasorelaxation. However, inhibiting BKCa channels was equally effective in reducing the beta-adrenergic vasorelaxation. The beta-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 beta-adrenergic vasorelaxation. Although inhibition and activation of K(V)7 channels or BKCa channels significantly changed baseline RBF in vivo, none of the treatments affected beta-adrenergic vasodilatation. In isolated segmental arteries, however, inhibition of K(V)7 and BKCa channels significantly reduced the beta-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.