The effects of alpha 1-adrenoceptor blockade and angiotensin converting enzyme inhibition on central and brachial blood pressure and vascular reactivity: the doxazosin-ramipril study

Andreas Jekell, Majid Kalani, Thomas Kahan, Andreas Jekell, Majid Kalani, Thomas Kahan

Abstract

We aimed to study whether inhibition of the renin-angiotensin-aldosterone system has effects on vascular structure and function beyond the effects on blood pressure reduction alone. Patients with mild-to-moderate hypertension (n = 61, age 54 ± 12 years, 34% women) received the angiotensin converting enzyme inhibitor ramipril 10 mg or the alpha 1-adrenoceptor blocker doxazosin 8 mg double-blind for 12 weeks. Aortic blood pressure, pulse wave velocity, and augmentation index were assessed by applanation tonometry. Endothelial function was studied by forearm post-ischemic flow mediated vasodilatation and by pulse wave analysis with beta 2-adrenoceptor agonist stimulation. Skin microvascular reactivity was assessed by laser Doppler fluxmetry and iontophoresis. Treatment with doxazosin or ramipril reduced aortic and brachial blood pressures (all P < 0.001), with greater reductions in aortic than brachial systolic blood pressures (P = 0.021) and aortic/brachial pulse pressure ratio (P = 0.005). Compared to doxazosin, ramipril reduced carotid-femoral and carotid-radial pulse wave velocity (both P < 0.05). Forearm endothelial dependent and independent vasodilatation, assessed by post-ischemic flow mediated vasodilatation and glyceryl trinitrate, and by pulse wave analysis remained unchanged by both doxazosin and ramipril. In addition, skin microvascular endothelial dependent (acetylcholine) and independent vasodilatation (sodium nitroprusside) remained unchanged. In conclusion, ramipril reduced indices of aortic stiffness, suggesting that angiotensin converting enzyme inhibitor therapy may have effects beyond blood pressure reduction. However, treatment did not appear to influence endothelial function. Evidence of endothelial dysfunction and its possible improvement by antihypertensive treatment might require more advanced hypertension.This study is registered at ClinicalTrials.gov (NCT02901977) and at EudraCT (# 2007-000631-25).

Keywords: Arterial stiffness; Blood pressure; Endothelial function; Renin-angiotensin-aldosterone system; Treatment.

Conflict of interest statement

Conflict of interest

This study was funded by the Swedish Heart–Lung Foundation (20130467), Karolinska Institutet Research Foundations (2014FoBi41054), and by an unrestricted Grant from Pfizer Inc. The authors have no further conflicts of interest to declare.

Ethical approval

The Regional Ethics Committee in Stockholm approved of the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Oral and written informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Relative changes (mean values ± SEM) in BP and vascular function by treatment. Significant treatment induced changes between groups are shown as *P < 0.05. Further statistical evaluation is presented in Table 2

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