TY - JOUR

T1 - No apparent role for T-type Ca2+ channels in renal autoregulation

AU - Frandsen, Rasmus Hassing

AU - Salomonsson, Max

AU - Hansen, Pernille B. Lærkegaard

AU - Jensen, Lars Jørn

AU - Braunstein, Thomas Hartig

AU - von Holstein-Rathlou, Niels-Henrik

AU - Sørensen, Charlotte Mehlin

PY - 2016

Y1 - 2016

N2 - Renal autoregulation protects glomerular capillariesagainst increases in renal perfusion pressure (RPP). Inthe mesentery, both L- and T-type calcium channels are involvedin autoregulation. L-type calcium channels participatein renal autoregulation, but the role of T-type channels is notfully elucidated due to lack of selective pharmacological inhibitors.The role of T- and L-type calcium channels in theresponse to acute increases in RPP in T-type channel knockoutmice (CaV3.1) and normo- and hypertensive rats was examined.Changes in afferent arteriolar diameter in the kidneysfrom wild-type and CaV3.1 knockout mice were assessed.Autoregulation of renal blood flow was examined duringacute increases in RPP in normo- and hypertensive rats underpharmacological blockade of T- and L-type calcium channelsusing mibefradil (0.1 μM) and nifedipine (1 μM). In contrastto the results from previous pharmacological studies, geneticdeletion of T-type channels CaV3.1 did not affect renal autoregulation.Pharmacological blockade of T-type channelsusing concentrations of mibefradil which specifically blocksT-type channels also had no effect in wild-type or knockoutmice. Blockade of L-type channels significantly attenuatedrenal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channelshad no effect on changes in the renal vascular resistanceafter acute increases in RPP in normo- and hypertensive rats.These findings show that genetic deletion of T-type channelsCaV3.1 or treatment with low concentrations of mibefradildoes not affect renal autoregulation. Thus, T-type calciumchannels are not involved in renal autoregulation in responseto acute increases in RPP.

AB - Renal autoregulation protects glomerular capillariesagainst increases in renal perfusion pressure (RPP). Inthe mesentery, both L- and T-type calcium channels are involvedin autoregulation. L-type calcium channels participatein renal autoregulation, but the role of T-type channels is notfully elucidated due to lack of selective pharmacological inhibitors.The role of T- and L-type calcium channels in theresponse to acute increases in RPP in T-type channel knockoutmice (CaV3.1) and normo- and hypertensive rats was examined.Changes in afferent arteriolar diameter in the kidneysfrom wild-type and CaV3.1 knockout mice were assessed.Autoregulation of renal blood flow was examined duringacute increases in RPP in normo- and hypertensive rats underpharmacological blockade of T- and L-type calcium channelsusing mibefradil (0.1 μM) and nifedipine (1 μM). In contrastto the results from previous pharmacological studies, geneticdeletion of T-type channels CaV3.1 did not affect renal autoregulation.Pharmacological blockade of T-type channelsusing concentrations of mibefradil which specifically blocksT-type channels also had no effect in wild-type or knockoutmice. Blockade of L-type channels significantly attenuatedrenal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channelshad no effect on changes in the renal vascular resistanceafter acute increases in RPP in normo- and hypertensive rats.These findings show that genetic deletion of T-type channelsCaV3.1 or treatment with low concentrations of mibefradildoes not affect renal autoregulation. Thus, T-type calciumchannels are not involved in renal autoregulation in responseto acute increases in RPP.

KW - Faculty of Health and Medical Sciences

KW - renal blood flow

KW - Autoregulation

KW - Calcium channel

KW - Renal vascular resistance

U2 - 10.1007/s00424-015-1770-9

DO - 10.1007/s00424-015-1770-9

M3 - Journal article

C2 - 26658945

VL - 468

SP - 541

EP - 550

JO - Pflügers Archiv - European Journal of Physiology

JF - Pflügers Archiv - European Journal of Physiology

SN - 0031-6768

IS - 4

ER -