The inhibition of aldosterone activity is a significant approach for preventing the progression of cardiovascular diseases in hypertensive patients. We hypothesized that N-type calcium channels might regulate aldosterone biosynthesis and firstly examined in vivo studies using rats. We investigated the effects of cilnidipine, an L-/N-type calcium channel blocker (CCB), and nifedipine, an L-type CCB, on aldosterone levels and found that only cilinidipine significantly reduced aldosterone levels. We secondly examined the direct relationship between N-type calcium channels and aldosterone production in human adrenocortical cells. In this study, the analysis of quantitative reverse transcription-PCR, western blotting, and immunocytological staining indicated the possible presence of N-type calcium channels in human H295R cell line. Patch clamp analysis indicated that omega-conotoxin GVIA (CnTX), an N-type calcium channel inhibitor, suppressed voltage-dependent barium currents. CnTX significantly reduced the transient calcium signaling induced by angiotensin II (Ang II) and partially prevented Ang II-induced aldosterone formation. Knockdown of α1B calcium channel subunits significantly decreased Ang II-induced aldosterone formation with increments in CYP11B2 mRNA expression. We investigated the inhibitory activities of cilnidipine and showed a dose-dependent inhibition effect on Ang II-induced aldosterone production. These results suggest that N-type calcium channels have a significant role in transducing the Ang II signal for aldosterone biosynthesis in humans.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.