Liquorice ingestion attenuates vasodilatation via exogenous nitric oxide donor but not via β2-adrenoceptor stimulation

Abstract

We examined the effect of liquorice ingestion on haemodynamic responses to exogenous nitric oxide donor (nitroglycerin) and β2-adrenoceptor agonist (salbutamol), and 11β-hydroxysteroid dehydrogenase activity, in 21 volunteers and 21 reference subjects. Haemodynamic data was captured before and after sublingual nitroglycerin (0.25 mg) and inhaled salbutamol (400 μg) during orthostatic challenge utilising radial pulse wave analysis and whole-body impedance cardiography. The recordings were performed at baseline and following two weeks of liquorice intake (290-370 mg/d glycyrrhizin). Urinary cortisone and cortisol metabolites were examined. Liquorice intake elevated aortic systolic and diastolic blood pressure and systemic vascular resistance when compared with the reference group. Following research drug administration the liquorice-induced increase in systemic vascular resistance was observed in the presence of nitroglycerin (p<0.05) but no longer in the presence of salbutamol. Liquorice ingestion decreased cardiac chronotropic response to upright posture (p = 0.032) in unadjusted analysis, but when adjusted for age and sex the difference in the upright change in heart rate was no longer significant. The urinary cortisone to cortisol metabolite ratio decreased from 0.70 to 0.31 (p<0.001) after liquorice intake indicating significant inhibition of the 11β-hydroxysteroid dehydrogenase type 2. In the reference group the haemodynamic variables remained virtually unchanged. These results suggest that liquorice exposure impaired vasodilatation in vivo that was induced by exogenous nitric oxide donor but not that induced by β2-adrenoceptor stimulation. Trial registration: EU Clinical Trials Register 2006-002065-39 ClinicalTrials.gov NCT01742702.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. The CONSORT flow diagram of study participants.

Fig 2. Aortic blood pressure at baseline and after the follow-up (reference group) or intervention (liquorice ingestion).

Systolic (a, b) and diastolic (c, d) blood pressure were measured in the absence (0–15 min) and presence (16–30 min) of sublingual nitroglycerin during supine position and orthostatic challenge. The passive head-up tilt was carried out from 5 to 10 min, and 20 to 25 min. Mean and standard error of the mean, statistical analyses compared the difference of the area under the curve between visit 1 and visit 2 in the liquorice versus the reference group, adjusted for age and sex.

Fig 3. Heart rate and augmentation index in the absence and presence of sublingual nitroglycerin.

Heart rate (a, b) and augmentation index (c, d) were measured at baseline and after the follow-up. Mean and standard error of the mean, the difference of the area under the curve between visit 1 and visit 2 was compared in the liquorice versus the reference group, adjusted for age and sex.

Fig 4. Liquorice intake and urinary glucocorticoid excretion.

The urinary ratio of tetrahydrocortisone to tetrahydrocortisol at baseline and after two weeks of liquorice ingestion, grey lines depict each individual, thick black line depicts mean values, n = 22.

Fig 5. Cardiac index and systemic vascular resistance index in the absence and presence of sublingual nitroglycerin.

Cardiac index (a, b) and systemic vascular resistance index (c, d) were measured at baseline and after the follow-up. Mean and standard error of the mean, the difference of the area under the curve between visit 1 and visit 2 was compared in the liquorice versus the reference group, adjusted for age and sex.

Fig 6. Heart rate and augmentation index in the absence and presence of salbutamol inhalation.

Heart rate (a, b) and augmentation index (c, d) were measured at baseline and after the follow-up. Mean and standard error of the mean, the difference of the area under the curve between visit 1 and visit 2 was compared in the liquorice versus the reference group, adjusted for age and sex.

Fig 7. Cardiac index and systemic vascular resistance index in the absence and presence of salbutamol inhalation.

Cardiac index (a, b) and systemic vascular resistance index (c, d) were measured at baseline and after the follow-up. Mean and standard error of the mean, the difference of the area under the curve between visit 1 and visit 2 was compared in the liquorice versus the reference group, adjusted for age and sex.

Fig 8. Summary of the mechanisms of liquorice-induced elevation in blood pressure.