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Effect of antihypertensive treatment on microvascular structure, central blood pressure and oxidative stress in patients with mild essential hypertension

De Ciuceis, Carolinaa; Salvetti, Massimoa; Rossini, Claudiaa; Muiesan, Maria Lorenzaa; Paini, Annaa; Duse, Sarahb; La Boria, Elisaa; Semeraro, Francescob; Cancarini, Annab; Rosei, Claudia Agabitia; Sarkar, Annamariaa; Ruggeri, Giuseppinac; Caimi, Luigic; Ricotta, Dorisc; Rizzoni, Damianoa; Rosei, Enrico Agabitia

doi: 10.1097/HJH.0000000000000067
ORIGINAL PAPERS: Oxidative stress

Background: It has been previously demonstrated that dihydropyridine calcium channel blockers may possess antioxidant properties and might improve vascular structure. Combination treatment with an angiotensin-converting enzyme inhibitor may have additional advantages, compared with a thiazide diuretic, in this regard. The aim of the present study was, therefore, to investigate the effects of a short-term treatment with lercanidipine, and to compare two combination treatments: lercanidipine + enalapril vs. lercanidipine + hydrochlorothiazide on structural alterations in retinal arterioles, on skin capillary density and on large artery distensibility.

Patients and methods: Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine 20 mg per day orally. Then they were treated for 6 months with lercanidipine + enalapril (n = 10) or lercanidipine + hydrochlorothiazide (n = 10) combinations. Investigations were performed in basal condition, after appropriate washout of previous treatments, after 4 weeks of lercanidipine monotherapy treatment, and at the end of the combination treatment. Non-invasive measurements of wall-to-lumen ratio (W/L) and other morphological parameters of retinal arterioles using scanning laser Doppler flowmetry were performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). Capillary density was evaluated by capillaroscopy, whereas pulse wave velocity and central blood pressure were assessed by the Sphygmo-Cor device (AtCor Medical West Ryde, Australia).

Results: A significant improvement of W/L and of other indices of retinal artery structure was observed after treatment with lercanidipine alone, with a further improvement after treatment with lercanidipine + enalapril, whereas after treatment with lercanidipine + hydrochlorothiazide the improvement was no longer observed. A similar behaviour was observed for central SBP and DBP. Capillary density was increased only after treatment with lercanidipine + enalapril.

Conclusion: Lercanidipine both in monotherapy and in combination with enalapril, was able to improve microvascular structure and to decrease central blood pressure, being thus a useful approach for both reducing blood pressure and improving vascular alterations in hypertension.

aClinica Medica, Department of Clinical and Experimental Sciences

bChair of Ophthalmology

cChair of Clinical Biochemistry, University of Brescia, Italy

Correspondence to Professor Damiano Rizzoni, Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, c/o 2a Medicina, Spedali Civili, 25100 Brescia, Italy. Tel: +39 030 396044; fax: +39 030 3384348; e-mail:

Abbreviations: ABPM, 24-h ambulatory blood pressure monitoring; ACE, angiotensin-converting enzyme; AIx, augmentation index; CRP, C-reactive protein; IL-18, interleukin-18; LPO, lipid peroxidation; MCP-1, macrophage chemotactic factor-1; MDA, malonyldialdehyde; PAI-1, plasminogen activator inhibitor-1; PVW, pulse wave velocity; RAS, renin–angiotensin system; sICAM-1, soluble inter-cellular adhesion molecule 1; sVCAM-1, soluble vascular cell adhesion molecule 1

Received 16 July, 2013

Revised 31 October, 2013

Accepted 31 October, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins