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).

Effects of Angiotensin-Converting Enzyme Inhibitors on Arterial Stiffness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Cardiovascular erapeutics [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]. e results of study-selection process are presented in Figure 1.…”

The interrelation of endothelial function and microvascular reactivity in different vascular beds, and risk assessment in hypertension: results from the Doxazosin–ramipril study

“…The Doxazosin–ramipril study included women and men 18 years or older with untreated mild-to-moderate primary hypertension (office systolic blood pressure 141–180 mmHg and/or diastolic blood pressure 91–110 mmHg) to evaluate the effects of treatment with ramipril or doxazosin during 12 weeks on vascular function, as described in detail elsewhere [ 29 ]. Patients with ischemic heart disease, congestive heart failure, arrhythmias, or diabetes mellitus were excluded.…”

“…PWA was assessed by applanation tonometry (Millar Instruments, Houston, TX, US) and the SpygmoCor device (AtCor Pty Ltd, West Ryde, NSW, Australia), as described previously [ 29 ]. From radial applanation tonometry, the central aortic waveform was calculated using a general transfer function by the device software, and central blood pressure was derived.…”

“…FMD was measured by post-ischemic hyperaemia in the non-dominant arm, as previously described [ 29 ]. Resting basal diameter of the brachial artery was measured for 1 min by a Vivid 7 Dimension ultrasound device with a 9 MHz linear transducer (GE Medical System, Horten, Norway).…”

Studies on the Kinetics of Doxazosin Degradation in Simulated Environmental Conditions and Selected Advanced Oxidation Processes

“…Doxazosin mesylate [(4-amino-6,7-dimethoxy-2quinazolinyl)-4-(1,4-benzodioxan-2-yl-carbonyl)-piperazine monomethansulphonate] ( Figure 1) belongs to the group of (α 1 )-adrenoreceptor antagonists [17]. It is used for the treatment of benign prostatic hyperplasia [17,18] and blood hypertension [18]. It is well absorbed by the digestive tract after oral administration.…”