Eur J Clin Pharmacol(1981) 20:251-258 European Journal of Clinical Pharmacology © Springer-Verlag 1981 Correlation Between Propranolol in Plasma and Urine, Renin-Aldosterone System and Blood Pressure in Essential Hypertension E. B. Pedersen, H. J. Kornerup, O. L. Pedersen, F. Andreasen, and P. Bjerregaard Department of MedicineC, Aarhus Kommunehospital, Department of Internal MedicineI, Aarhus Amtssygehus, and Divisionof ClinicalPharmacology, Instituteof Pharmacology, University of Aarhus, Denmark Summary. Thirty patients with mild or moderate essential hypertension, and a fixed elevation of dia- stolic blood pressure, were randomly allocated to three groups and treated with propranolo140 mg x 4 (Group 1), 80rag x 4 (Group 2) and 160mg x 4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h uri- nary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradu- ally increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treat- ment. The maximum reduction in diastolic BP occur- red after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduc- tion was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA and PAC fell in all groups, and remained reduced during C and D in Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin-aldos- terone system was initially suppressed in all groups, but for unknown reasons it increased towards the control level after seven to eleven weeks of therapy with 320 and 640 mg/day, and that the reduction in systolic BP increased with higher doses of prop- ranolol and with increasing urinary propranolol excretion. Key words: aldosterone, hypertension, propranolol; blood pressure, plasma level, renin, urine level The antihypertensive effect of propranolol is well documented, but the mechanism behind the blood pressure reduction is unknown. Changes in cardiac output, resetting of baroreceptors, adaptation of the peripheral vascular resistance, changes in the renin- aldosterone system and a central nervous system - mediated effect have all been suggested as the expla- nation for the blood pressure reduction (Lewis 1976; Lorimer et al. 1976). According to Hollifield et al. (1976) reduction in blood pressure by a dose of 160 mg daily could be attributed to changes in the renin-aldosterone system, whereas an effect via the central nervous system was involved when larger doses were used. There are several reports of measurement of total propranolol in plasma, and of the activity of the renin-aldosterone system in essential hypertension during propranolol therapy. However, systematic studies over several weeks, with repeated simultane- ous, determinations of total- and free propranolol in plasma and urine, plasma renin activity, plasma aldosterone concentration and blood pressure, and analysis of the relationship between these parame- ters, are not available at relatively high doses of propranolol, i.e. exceeding 160 mg daily. It was the purpose of the present investigation to measure (1) blood pressure (BP), (2) pulse rate (PR), (3) plasma renin activity (PRA) and plasma aldosterone concentration (PAC), (4) total plasma 0031-6970/81/0020/0251/$01.60