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).
Highlights
Hypertension is characterized by an increased sympathetic vascular tone, early vascular remodelling of small resistance arteries, and impaired endothelial function [1,2,3]
Aortic dilatation, increased aortic stiffness, augmentation index (AIx), and central pulse pressure are associated with endothelial dysfunction of conduit arteries [7,8,9,10], and
Angiotensin converting enzyme (ACE) inhibitors appear to reduce arterial stiffness independent of their ability to reduce blood pressure (BP), but it remains unclear whether they are superior to other antihypertensive drug classes; and the effects of alpha 1-adrenoceptor blockers have not been well studied [22, 23]
Summary
Hypertension is characterized by an increased sympathetic vascular tone, early vascular remodelling of small resistance arteries, and impaired endothelial function [1,2,3]. Aortic dilatation, increased aortic stiffness, AIx, and central pulse pressure are associated with endothelial dysfunction of conduit arteries [7,8,9,10], and. ACE inhibitors appear to reduce arterial stiffness independent of their ability to reduce BP, but it remains unclear whether they are superior to other antihypertensive drug classes; and the effects of alpha 1-adrenoceptor blockers have not been well studied [22, 23]. We compared the effects of blocking the RAAS by the ACE inhibitor ramipril to reducing noradrenergic sympathetic vascular tone by the alpha 1-adrenoceptor blocker doxazosin in patients with uncomplicated mild-to-moderate hypertension. We assessed central BP and indices of aortic stiffness by pulse wave analysis, and endothelial function was examined by several methods in the forearm skeletal muscle and in the skin microcirculation, to reflect both conduit and resistance artery function
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