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

• Published in: Pflügers Archiv 2016-04, Vol.468 (4), p.541-550
• Main Authors: Frandsen, Rasmus Hassing, Salomonsson, Max, Hansen, Pernille B. L., Jensen, Lars J., Braunstein, Thomas Hartig, Holstein-Rathlou, Niels-Henrik, Sorensen, Charlotte Mehlin
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Calcium Channel Blockers - pharmacology; Calcium Channels, T-Type - genetics; Calcium Channels, T-Type - metabolism; Cell Biology; Gene Deletion; Homeostasis; Human Physiology; Integrative Physiology; Kidney - blood supply; Kidney - metabolism; Kidney - physiology; Mibefradil - pharmacology; Mice; Mice, Inbred C57BL; Molecular Medicine; Neurosciences; Receptors; Renal Circulation
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-015-1770-9

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 (Ca V 3.1) and normo- and hypertensive rats was examined. Changes in afferent arteriolar diameter in the kidneys from wild-type and Ca V 3.1 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 Ca V 3.1 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 Ca V 3.1 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.