Renovascular BKCachannels are not activated in vivo under resting conditions and during agonist stimulation

Abstract

We investigated the role of large-conductance Ca2+-activated K+(BKCa) channels for the basal renal vascular tone in vivo. Furthermore, the possible buffering by BKCaof the vasoconstriction elicited by angiotensin II (ANG II) or norepinephrine (NE) was investigated. The possible activation of renal vascular BKCachannels by cAMP was investigated by infusing forskolin. Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry or ultrasonic Doppler. Renal preinfusion of tetraethylammonium (TEA; 3.0 μmol/min) caused a small reduction of baseline RBF, but iberiotoxin (IBT; 0.3 nmol/min) did not have any effect. Renal injection of ANG II (1–4 ng) or NE (10–40 ng) produced a transient decrease in RBF. These responses were not affected by preinfusion of TEA or IBT. Renal infusion of the BKCaopener NS-1619 (90.0 nmol/min) did not affect basal RBF or the response to NE, but it attenuated the response to ANG II. Coadministration of NS-1619 with TEA or IBT abolished this effect. Forskolin caused renal vasodilation that was not inhibited by IBT. The presence of BKCachannels in the preglomerular vessels was confirmed by immunohistochemistry. Despite their presence, there is no indication for a major role for BKCachannels in the control of basal renal tone in vivo. Furthermore, BKCachannels do not have a buffering effect on the rat renal vascular responses to ANG II and NE. The fact that NS-1619 attenuates the ANG II response indicates that the renal vascular BKCachannels can be activated under certain conditions.