Abstract
OBJECTIVE:The multidrug resistance P-glycoprotein (P-gp) has been shown to contribute to the secretion of aldosterone by human adrenal cells in vitro. To address the clinical relevance of this finding, we studied the impact of a loss of function P-gp polymorphism of ABCB1 gene and of clarithromycin, a P-gp inhibitor, on plasma aldosterone (PAC) and renin (PRC) concentrations in heathy subjects.
DESIGN AND METHOD:Three groups of 20 healthy normotensive male volunteers were selected on the basis of their ABCB1 genotypeCC non carriers, heterozygous CT and TT homozygous carriers of haplotype 2677–3435. PAC, PRC and urinary aldosterone excretionwere measured at 09:00 in semi-recumbent position and on ad libitum sodium diet at baseline and after 5-day treatment with the P-gp inhibitor, clarithromycin (200 MG bid).
RESULTS:Age, BMI, blood pressure, plasma Na and K concentrations, PAC and UAE (urinary adlosterone excretion) did not differ among the genotypes. There was a trend for an increase in PRC between CC, CT and TT subjects with a significantly higher PRC in TT than in CC subjects (mean difference+ 34% [95%CI%4–50%], p = 0.0295). PRC, PAC and UAE were not affected by clarithromycin in the CC group (p = 0.2746, 0.2860 and 0.2274, respectively), or in the CT and TT groups.(Figure is included in full-text article.)
CONCLUSIONS:The 2677–3435 P-gp haplotype and Pg-p inhibition were not associated with significant differences in aldosterone secretion in physiological conditions on a normal sodium intake in healthy subjects. The slightly higher PRC in homozygous carrier TT subjects than in non-carrier CC subjects may reflect a subtle impairment of aldosterone secretion. Whether this subtle abnormality on steady state may predict an impaired adaption of aldosterone secretion in pathophysiological conditions remains to be established.