Pregnane X receptor activator rifampin increases blood pressure and stimulates plasma renin activity
Hassani‐Nezhad‐Gashti, Fatemeh; Salonurmi, Tuire; Hautajärvi, Heidi; Rysä, Jaana; Hakkola, Jukka; Hukkanen, Janne (2020-04-28)
Hassani‐Nezhad‐Gashti, F., Salonurmi, T., Hautajärvi, H., Rysä, J., Hakkola, J. and Hukkanen, J. (2020), Pregnane X Receptor Activator Rifampin Increases Blood Pressure and Stimulates Plasma Renin Activity. Clin. Pharmacol. Ther., 108: 856-865. https://doi.org/10.1002/cpt.1871
© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
https://creativecommons.org/licenses/by-nc/4.0/
https://urn.fi/URN:NBN:fi-fe2020112592982
Tiivistelmä
Abstract
We conducted a clinical trial with 22 healthy volunteers to investigate the effects of pregnane X receptor (PXR) agonist rifampin on blood pressure (BP). The study was randomized, crossover, single‐blind, and placebo‐controlled. Rifampin 600 mg or placebo once daily was administered for a week and the 24‐hour ambulatory BP was monitored at the end of each arm on the eighth day. Rifampin elevated the mean systolic and diastolic 24‐hour BP (4.7 mmHg, P < 0.0001, and 3.0 mmHg, P < 0.001, respectively) as well as the mean heart rate (3.5 bpm, P = 0.038). The serum renin concentration and the plasma renin activity were increased. Although rifampin increased circulating 4β‐hydroxycholesterol (4βHC) as expected, the plasma 4βHC concentration strongly negatively correlated with 24‐hour BP, especially systolic, in both rifampin and placebo arms (rifampin systolic BP, r = −0.69, P < 0.001; placebo systolic BP, r = −0.70, P < 0.001). The 4βHC, an agonist for liver X receptor (LXR), induced renin expression modestly in LXR‐α expressing Calu‐6 cells but only at unphysiologically high 4βHC concentrations. In conclusion, rifampin stimulates renin activity and has a hypertensive effect. This finding should be considered when designing interaction studies involving rifampin or other PXR agonists. Furthermore, PXR may represent a putative therapeutic target for the treatment of hypertension.
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