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

Abstract

Renal autoregulation protects glomerular capillaries against increases in renal perfusion pressure (RPP). In the mesentery, both L- and T-type calcium channels are involved in autoregulation. L-type calcium channels participate in renal autoregulation, but the role of T-type channels is not fully elucidated due to lack of selective pharmacological inhibitors. The role of T- and L-type calcium channels in the response to acute increases in RPP in T-type channel knockout mice (CaV3.1) and normo- and hypertensive rats was examined. Changes in afferent arteriolar diameter in the kidneys from wild-type and CaV3.1 knockout mice were assessed. Autoregulation of renal blood flow was examined during acute increases in RPP in normo- and hypertensive rats under pharmacological blockade of T- and L-type calcium channels using mibefradil (0.1 μM) and nifedipine (1 μM). In contrast to the results from previous pharmacological studies, genetic deletion of T-type channels CaV3.1 did not affect renal autoregulation. Pharmacological blockade of T-type channels using concentrations of mibefradil which specifically blocks T-type channels also had no effect in wild-type or knockout mice. Blockade of L-type channels significantly attenuated renal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channels had no effect on changes in the renal vascular resistance after acute increases in RPP in normo- and hypertensive rats. These findings show that genetic deletion of T-type channels CaV3.1 or treatment with low concentrations of mibefradil does not affect renal autoregulation. Thus, T-type calcium channels are not involved in renal autoregulation in response to acute increases in RPP.

T-type Ca2+channels and autoregulation of local blood flow

“…99 In isolated kidneys from mice lacking the expression of Ca V 3.1 we showed that T-type channels play no apparent role in the afferent arteriolar autoregulation at renal perfusion pressures between 75 and 155 mmHg. 61 Also, in normo -and hypertensive rats the changes in RBF after acute increases in renal perfusion pressure was identical in saline-treated and mibefradil-treated rats. 61 The concentration of mibefradil used in this study is suggested to be specific for T-type channels but nevertheless these results have to be interpreted with caution.…”

“…61 Also, in normo -and hypertensive rats the changes in RBF after acute increases in renal perfusion pressure was identical in saline-treated and mibefradil-treated rats. 61 The concentration of mibefradil used in this study is suggested to be specific for T-type channels but nevertheless these results have to be interpreted with caution. 100 Taken together it appears as there is no major role for T-type channels in the renal autoregulation at pressures within the physiologic range.…”

“…61,80,92,93 However, recent findings from T-type knockout mice showed that lack of Ca V 3.1 led to increased renal blood flow (RBF) whereas lack of Ca V 3.2 led to increased glomerular filtration rate (GFR). 94 This suggests that Ca V 3.1 maintains afferent tone whereas Ca V 3.2 supports efferent dilatation.…”

“…60 Thus, the exact function of Ca V 3.1 and Ca V 3.2 channels in the resistance vasculature is currently under investigation using knockout mice. 46,50,[61][62][63][64] …”

Role of renal vascular potassium channels in physiology and pathophysiology

“…The dominating VOCC in most vascular beds, among them renal, is the dihydropyridine sensitive L‐type channel (Ca V 1.2) . Furthermore, T‐type channels have been found in several vascular beds including renal pre‐ and post‐glomerular arterioles, but their role is debated and remains to be fully elucidated . As renal VSMC V m is mainly determined by K + channels in these cells, they may have an important impact on the salt and water balance and thus blood pressure.…”