Lymphocyte beta 2-receptor activity, metoprolol kinetics, and response to metoprolol in hypertensive black men

To evaluate whether variability in S-metoprolol kinetics and lymphocyte beta 2-receptor-mediated cyclic adenosine monophosphate (cAMP) accumulation is related to the variability in antihypertensive response to metoprolol of black men.

Prospective, unblinded study.

University-based preventive medicine clinic.

Twelve hypertensive black men.

Ambulatory blood pressure was measured over 24 hours before and after metoprolol administration. Ex vivo responsiveness of lymphocyte beta 2-receptors to isoproterenol was established for each subject before initiating metoprolol therapy. Plasma samples were collected over 12 hours at the conclusion of the study, from which metoprolol enantiomer concentrations were determined by chiral high-performance liquid chromatography, and kinetic values were calculated. The 24-hour ambulatory blood pressure responses to metoprolol were highly variable, with systolic blood pressure responses ranging from -13 to +33 mm Hg and diastolic blood pressure responses ranging from -15 to +15 mm Hg. There was a significant relationship between the metoprolol-induced change in systolic blood pressure and the maximum lymphocyte beta 2-receptor cAMP production (y = 0.47x-7.79; r2 = 0.49, p < 0.05) such that those with the highest maximum cAMP production had the greatest blood pressure increases during metoprolol therapy. There was no relationship between S-metoprolol concentration and blood pressure response. Mean oral clearance values for S- and R-metoprolol were 1320 and 2346 ml/minute, respectively.

Lymphocyte beta 2-receptor data suggest that individuals most responsive to beta-receptor stimulation may be at greatest risk of blood pressure elevation during beta 2-receptor blockade. The metoprolol enantiomer kinetic data are markedly different from previously published data and may represent racial differences in pharmacokinetics.