Pregnane X Receptor Activator Rifampin Increases Blood Pressure and Stimulates Plasma Renin Activity.

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.