Antihypertensive effect of atenolol alone or combined with chlorthalidone in patients with essential hypertension

1 The effect of atenolol, a cardioselective β-adrenoceptor acting drug, was studied alone or combined with chlorthalidone on blood pressure, heart rate, systolic time intervals, limb blood flow and limb vascular resistance. Plasma renin activity and plasma atenolol levels were also measured in the study.

2 Supine blood pressure was reduced in group A (11 patients) from 169.4 ± 5.06/111.2 ± 2.63 mmHg to 136.9 ± 2.55/90.9 ± 1.19 mmHg (P < 0.001) during the administration of atenolol alone. Concomitantly supine heart rate was decreased from 83.9 ± 4.10 beats/min to 59.7 ± 1.67 beats/min (P < 0.01) — 4th week. After the administration of atenolol over 8 weeks, supine blood pressure was 138.6 ± 1.21/94.4 ± 2.12 mmHg and supine heart rate was 59.5 ± 2.05 beats/min.

3 Supine blood pressure was reduced in group B (27 patients) from 183.6 ± 4.58/118.7 ± 2.01 mmHg (mean ± s.e. mean of systolic and diastolic blood pressure) to 171.3 ± 4.08/108.9 ± 2.26 mmHg (P < 0.01) during the administration of atenolol alone. Concomitantly supine heart rate was decreased from 84.0 ± 1.89 to 68.7 ± 1.94 (P < 0.001) beats/min. When atenolol was combined with chlorthalidone, supine blood pressure was reduced from 171.3 ± 4.08/108.9 ± 2.26 mmHg to 143.5 ± 3.68/94.8 ± 2.63 mmHg (P < 0.001). Heart rate did not alter significantly with the addition of chlorthalidone.

4 After the administration of atenolol alone in 12 patients of group B, there was a decrease of mean blood pressure from 131.8 ± 2.88 (mean ± s.e. mean) mmHg to 119.0 ± 4.05 mmHg (P < 0.001); of heart rate from 76.4 ± 3.58 beats/min to 57.0 ± 2.55 beats/min (P < 0.001); of calf blood flow from 9.23 ± 1.39 ml 100 g^-1 min^-1 to 5.05 ± 0.89 ml 100 g^-1 min^-1 (P < 0.001); and an increase of calf vascular resistance from 16.54 ± 1.90 (mmHg min^-1 100 g^-1)/ml to 28.53 ± 3.40 (mmHg min^-1 100 g^-1)/ml (P < 0.005). Atenolol did not alter significantly pre-ejection period index (P < 0.1). In atenolol-treated patients upon addition of chlorthalidone, there was a further decrease of mean blood pressure from 119.0 ± 4.05 mmHg to 105.9 ± 4.12 mmHg (P < 0.001). There were no further significant alterations of heart rate, pre-ejection period index, calf blood flow, and calf vascular resistance (P> 0.01).

5 Atenolol decreased plasma renin activity from 4.69 ± 0.87 to 2.85 ± 0.68 ng ml^-1 h^-1 (P < 0.05), and chlorthalidone increased it from 2.85 ± 0.68 to 3.81 ± 0.98 ng ml^-1 h^-1 (P < 0.05). Plasma renin activity on atenolol plus chlorthalidone was not significantly different from that on placebo (P> 0.1).

6 There was a 7.8 fold-interindividual variability in the relationship between plasma atenolol concentrations and the atenolol dose upon administration of a single oral dose of 100 mg.