Evaluation of Aldosterone Suppression by Cinnarizine, a Putative Cav1.3 Inhibitor
Authors' conclusion
A Cav1.3 ligand, cinnarizine, reduced aldosterone secretion from adrenocortical cells, but at maximum-soluble concentrations was less effective than the nonselective calcium blocker, nifedipine. At clinical doses, cinnarizine did not reduce plasma ARR in patients with PA, and, as in vitro, was inferior to nifedipine. The limited efficacy of high-dose nifedipine may be due to incomplete Cav1.3 blockade, or to a role for non-L-type calcium channels in aldosterone secretion.
Study context
- Population
- Adults with primary aldosteronism (PA); angiotensin II-stimulated HAC15 adrenocortical cells in vitrocrossover
- Participants
- 15 adults
- Exposure
- Cinnarizine vs nifedipine
- Outcome
- Hierarchical:
- Change in ARR
- Urinary tetrahydroaldosterone (THA)
- Plasma aldosterone concentration (PAC)
- Follow-up
- 2 weeks
Methodological detailsprospective, open-label, 2-week washout
- Prospective
- Open-label
- 2-week washout
Main finding
As reported in the abstract
F
3.25
P = 0.047
Aldosterone-to-renin ratio (ARR) reduced by nifedipine but not cinnarizine
F
4.77
P = 0.013
Plasma aldosterone concentration (PAC) rose with both drugs
Observational data: associations, not effects.
Secondary outcomes
Mean
| Outcome | Cinnarizine | Nifedipine |
|---|---|---|
| In vitro fold change of aldosterone concentrations (mean change ± SEM) | −0.47 (SE 0.05) | −0.59 (SE 0.05) |
| In vitro fold change of CYP11B2 expression (mean change ± SEM) | −0.56 (SE 0.07) | −0.78 (SE 0.07) |
- In vitro fold change of aldosterone concentrations (mean change ± SEM): cinnarizine 30 μM; nifedipine 100 μM
- In vitro fold change of CYP11B2 expression (mean change ± SEM): cinnarizine 30 μM; nifedipine 100 μM
Original publication
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