Cardiovascular oxidative stress is reduced by an ACE inhibitor in a rat model of streptozotocin-induced diabetes

Fabio Fiordaliso, Ivan Cuccovillo, Roberto Bianchi, Antonio Bai, Mirko Doni, Monica Salio, Noeleen De Angelis, Pietro Ghezzi, Roberto Latini, Serge Masson

Research output: Contribution to journalArticlepeer-review

Abstract

Blockade of the renin-angiotensin system (RAS) reduces cardiovascular morbidity and mortality in diabetic patients. Ang II-mediated generation of reactive oxygen species (ROS) has been suggested to be involved in several diabetic complications. We investigated whether the inhibition of Ang II production with an ACE inhibitor (ACEi) reduces oxidative stress and limits structural cardiovascular remodeling in a rat model of streptozotocin (STZ)-induced diabetes. Diabetic rats were treated for 7 weeks with an ACEi (lisinopril, 5 mg/kg/d), an antioxidant (N-acetyl-l-cysteine (NAC), 0.5 g/kg/d) and their combination. At sacrifice, ROS in the myocardium and thoracic aorta, LV myocyte number and size and aorta morphology were determined by quantitative histological methods. Superoxide and hydroxyl radical content, detected by dihydroethidium (DHE) and 8-hydroxydeoxyguanosine (8-OHdG), were 6.7 and 4.5-fold, respectively, higher in diabetic myocardium than in non-diabetic controls (p <0.001). The amount of superoxide was 5-fold higher in the thoracic aorta of diabetic rats compared to controls (p <0.001). Diabetes caused a modest increase in myocyte volume (+ 13%, p <0.01), a reduction of LV myocyte number (- 43%, p <0.001), an accumulation of collagen around coronary arterioles (1.9-fold increase, p <0.01) and a decrease in arterial elastin / collagen ratio (- 63%, p <0.001) compared to controls. Treatment with the ACEi attenuated ROS formation and prevented phenotypic changes in the heart (cardiomyocyte hypertrophy, perivascular fibrosis) and in the aorta of diabetic rats to the same extent as NAC. The absence of an additive effect, suggests a common mechanism of action, through the reduction of oxidative stress.

Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalLife Sciences
Volume79
Issue number2
DOIs
Publication statusPublished - Jun 6 2006

Keywords

  • Angiotensin-converting enzyme inhibitor (ACEi)
  • Diabetes
  • N-acetyl-l-cysteine (NAC)
  • Reactive oxygen species (ROS)
  • Streptozotocin

ASJC Scopus subject areas

  • Pharmacology

Fingerprint

Dive into the research topics of 'Cardiovascular oxidative stress is reduced by an ACE inhibitor in a rat model of streptozotocin-induced diabetes'. Together they form a unique fingerprint.

Cite this