Pregnane X Receptor Activator Rifampin Increases Blood Pressure and Stimulates Plasma Renin Activity.
Clin Pharmacol Ther
; 108(4): 856-865, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32344455
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 4ß-hydroxycholesterol (4ßHC) as expected, the plasma 4ßHC 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 4ßHC, an agonist for liver X receptor (LXR), induced renin expression modestly in LXR-α expressing Calu-6 cells but only at unphysiologically high 4ßHC 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.
Full text:
1
Database:
MEDLINE
Main subject:
Renin-Angiotensin System
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Rifampin
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Blood Pressure
/
Renin
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Pregnane X Receptor
Type of study:
Clinical_trials
Limits:
Adult
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Female
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Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
Clin Pharmacol Ther
Year:
2020
Type:
Article
Affiliation country:
Finland