Cardiovascular Research Advance Access published February 5, 2014 1

Hydrogen sulfide accounts for the peripheral vascular effects of zofenopril independently of ACE inhibition

Mariarosaria Bucci1,*, Valentina Vellecco1,*, Anna Cantalupo1,*, Vincenzo Brancaleone2, Zongmin Zhou3, Stefano Evangelista4, Vincenzo Calderone5, Andreas Papapetropoulos3, Giuseppe Cirino1 Department of Pharmacy, University of Naples “Federico II” Naples, Italy

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Department of Science, University of Basilicata, Italy

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Laboratory for Molecular Pharmacology, Department of Pharmacy, University of Patras,

Accepted Manuscript

Greece 4

Menarini Ricerche spa, Firenze, Italy

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Department of Pharmacy, University of Pisa, Pisa, Italy

Name and complete address for correspondence: Prof. Giuseppe Cirino, Via D. Montesano 49, 80131 Naples, Italy fax+39 081 678403, tel +39 081 679934, email: [email protected] *

Drs. M. Bucci, V. Vellecco and A. Cantalupo equally contributed to this article

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: [email protected].

Downloaded from http://cardiovascres.oxfordjournals.org/ at University of Windsor on July 2, 2014

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Abstract Aims Therapeutic use of sulfhydrylated inhibitor S-zofenopril has raised different hypotheses regarding the role played by its thiol group in the beneficial clinical effects exerted compared to other ACE inhibitors. Here, we investigated on H2S pathway as the accountable for extra-beneficial effects in vascular function. Methods & Results SHR and WKY rats were treated with either S-zofenopril or enalapril in vivo. Aorta and carotid were harvested and ex vivo vascular reactivity to Ach and L-

evaluated in both vascular tissues. The vascular response to Ach in both carotid and aorta was impaired in SHR (~30%, P

Hydrogen sulfide accounts for the peripheral vascular effects of zofenopril independently of ACE inhibition.

Therapeutic use of sulfhydrylated inhibitor S-zofenopril has raised different hypotheses regarding the role played by its thiol group in the beneficia...
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