University of Oulu

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.

Pregnane X receptor activator rifampin increases blood pressure and stimulates plasma renin activity

Saved in:
Author: Hassani‐Nezhad‐Gashti, Fatemeh1,2,3; Salonurmi, Tuire2,3,4; Hautajärvi, Heidi5;
Organizations: 1Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Oulu, Finland
2Biocenter Oulu, Oulu, Finland
3Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
4Research Unit of Internal Medicine, University of Oulu, Oulu, Finland
5Admescope Ltd., Oulu, Finland
6School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 12.7 MB)
Persistent link:
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2020-11-25


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.

see all

Series: Clinical pharmacology & therapeutics
ISSN: 0009-9236
ISSN-E: 1532-6535
ISSN-L: 0009-9236
Volume: 108
Issue: 4
Pages: 856 - 865
DOI: 10.1002/cpt.1871
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: The study was financially supported by grants from the Academy of Finland (grants 276747, 286743, and 323706), the Novo Nordisk Foundation (grants NNF14OC0010653 and NNF15OC0015846), the Finnish Medical Foundation, the Finnish Foundation for Cardiovascular Research, the Northern Finland Health Care Support Foundation, and the Diabetes Research Foundation.
Academy of Finland Grant Number: 286743
Detailed Information: 286743 (Academy of Finland Funding decision)
323706 (Academy of Finland Funding decision)
Copyright information: © 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.