title: 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.
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).
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.|Department of Cardiology, Danderyd University Hospital Corp, Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jekell
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Majid
authors.initials: M
authors.lastname: Kalani
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. thomas.kahan@sll.se.|Department of Cardiology, Danderyd University Hospital Corp, Stockholm, Sweden. thomas.kahan@sll.se.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0001-9909-4956
authors.initials: T
authors.lastname: Kahan
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination; D004311:Double-Blind Method; D017292:Doxazosin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D017257:Ramipril / Q000008:administration & dosage*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013548:Sweden; D016896:Treatment Outcome; D059289:Vascular Stiffness
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril; D017292:Doxazosin
keywords: Arterial stiffness; Blood pressure; Endothelial function; Renin-angiotensin-aldosterone system; Treatment