No apparent role for T-type Ca2+ channels in renal autoregulation
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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.
KeywordsRenal blood flow Autoregulation Calcium channel Renal vascular resistance
The skillful technical assistance of Ms. Cecilia Vallin, Ms. Nadia Soori, and Ms. Vibeke G. Christensen is gratefully acknowledged. We acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen.
Compliance with ethical standards
This study was supported by the Danish National Research Foundation, the A.P. Møller Foundation for the Advancement of Medical Sciences, and Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond.
Conflict of interest
The authors declare that they do not have competing interests.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.