Plasma renin substrate concentration during chronic propranolol therapy.

To THE EDITOR: The review by Gordon concerning a positive correlation between plasma renin substrate concentration (PRS) and blood pressure (BP) prompted us to evaluate our PRS data from a randomized double-blind study on the antihypertensive effect of enalapril (MK 421) compared to propranolol. Twenty-two patients with essential hypertension were treated in subsequent 4-week periods by placebo and 40, 80, and 120 mg b.i.d. propranolol (n = 9); or by placebo and 5, 10, and 20 mg b.i.d. enalapril (n = 13). If BP decreased insufficiently, 25 mg s.d.d. hydrochlorothiazide (HCT) was added to the highest dose (n = 7 and n = 10, respectively). At the end of each period (in the placebo period also after 2 weeks), before the morning dose was given (i.e., about 12 hours after the previous dose) and after 90 minutes of upright stimulation, blood samples were taken for determination of angiotensin I and II (AI and All), plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma converting enzyme activity (CEA), and PRS. The BP was measured by Arteriosonde. PR A (normal range 0.20 to 1.20 pmol/ liter/sec) and PAC (0.15 to 1.10 nmol/liter) were measured by standard radioimmunoassay techniques. AI (10 to 80 pmol/liter) and All (5 to 50 pmol/liter) were measured by radioimmunoassay after blood sampling with an inhibitor solution containing EDTA, captopril, and pepstatin, and a batch-wise Dowex resin extraction procedure. CEA (0.30 1.20 /nmol/liter/ sec) was measured by a colorimetric method, and PRS (0.90 to 1.05 /xmol/liter for men; 0.60 to 0.90 liter for women) by an antibody-trapping technique. Data were analyzed with Wilcoxon's test for paired observations. In table 1, the mean arterial pressure (MAP) and the geometric means of the hormonal parameters are shown. PR A and AI increased during enalapril therapy (p < 0.002), while PAC (p < 0.04) All, CEA (bothp < 0.002), and MAP (p < 0.005) decreased. PRS did not change at the lower doses, but decreased at the highest dose (p < 0.01) and with the combined therapy (p < 0.02). PRA, AI, and All decreased during propranolol treatment (p < 0.01), but returned to baseline values after the addition of HCT. MAP and PAC also decreased (p < 0.02, except for the lowest dose), and CEA did not change. In 13 of the 22 patients, the two pretreatment PRS concentrations were above the upper normal limit, which is in agreement with the observation of Walker et al. in hypertensive patients. During propranolol treatment, these high PRS levels increased even further (p < 0.01, except for lowest dose). We cannot explain this phenomenon, although a decrease in PRA cannot be the cause, as the increase in PRA after the addition of HCT still is accompanied by a high PRS. Thus, all changes in the parameters were in the expected directions, with the exception of PRS. Our findings of an increased PRS in the presence of a decreased BP after chronic propranolol therapy has to our knowledge not been reported earlier and is at variance with the causal relationship suggested by Gordon.'