Twenty patients with essential hypertension were randomised to a 7-week period of dose titration with doxazosin, 1-8mg/day or enalapril, 5-20mg/day. In a further 7-week period the dosage level reached with the initial drug was halved, and titration with the second agent was carried out. Blood pressure responses at the end of each treatment period were assessed by clinic measurements made 24 hours post-dose. In the first treatment period, enalapril (mean dose 19mg/day) reduced serum free ACE activity by 40% and had a greater effect than doxazosin (mean dose 5.2mg/day) on clinic supine blood pressure (systolic and diastolic). In the second period, the addition of enalapril to doxazosin was associated with a significant fall in clinic standing blood pressure (systolic and diastolic), despite the doxazosin dose reduction and consequent decrease in median plasma doxazosin concentration (from 10.6 to 5.2ng/ml). Alternatively, when doxazosin was added to enalapril, free ACE activity remained 40% decreased despite enalapril dose reduction, and blood pressure was not further affected. Plasma renin activity was increased by enalapril. No changes were observed in plasma aldosterone or lipid concentrations with either drug. The combination of doxazosin and enalapril was well tolerated and lowered blood pressure overall. Judged by clinic measurements 24 hours post-dose, most of the antihypertensive effect was attributable to the enalapril component. However, ambulatory blood pressure monitoring 0-12 hours post-dose in a subset of patients suggested a contribution of doxazosin earlier in the dose interval.
This study was to investigate the interaction between opposite result was obtained for clinic BP at trough, whereby the addition of amlodipine to perindopril low doses of perindopril (2 mg daily) and amlodipine (2.5 mg daily) on ambulatory blood pressure (BP), clinic reduced erect systolic BP (P = 0.036) and both supine and erect diastolic BP (P = 0.038) whereas the addition BP, serum angiotensin-converting enzyme (ACE), plasma levels of renin (PRA), angiotensin II (Ang II), of perindopril to amlodipine was without effect. The addition of perindopril to amlodipine decreased aldosterone, and atrial natriuretic peptide (␣-h ANP) in subjects with essential hypertension. The study design serum ACE by 72% and increased PRA two-fold, without change in plasma levels of Ang II, aldosterone or ␣-h was a parallel, two-period, placebo-controlled, doubleblind crossover design, with 11 subjects receiving per-ANP. The addition of amlodipine to perindopril increased plasma aldosterone 1.7-fold but did not affect indopril and 10 receiving amlodipine during the run-in phase.serum ACE, PRA, Ang II, or ␣-h ANP. These interactions between perindopril and amlodipThe addition of amlodipine to perindopril had no effect on ambulatory BP, whereas the addition of perinine may have been conditioned by the specific effects of the therapy first given, as well as by the different cirdopril to amlodipine reduced both systolic (P = 0.027) and diastolic (P = 0.049) ambulatory BP. By contrast, the cumstances of BP measurement (ambulatory vs clinic).
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