Effect of chronic pre-treatment with angiotensin converting enzyme inhibition on skeletal muscle mitochondrial recovery after ischemia/reperfusion

Fabien Thaveau, Joffrey Zoll, Jamal Bouitbir, Benoît N'Guessan, Philippe Plobner, Nabil Chakfe, Jean Georges Kretz, Ruddy Richard, François Piquard, Bernard Geny

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Impaired skeletal muscle energetic participates in peripheral arterial disease (PAD) patient's morbidity and mortality. Angiotensin converting enzyme inhibition (ACEi), cornerstone for pharmacologic risk factor management in PAD patients, might also be interesting by protecting skeletal muscle energetic. We therefore determined whether chronic ACEi might reduce ischemia-induced mitochondrial respiratory chain dysfunction in the frequent setting of hindlimb ischemia-reperfusion. Ischemic legs of rats submitted to 5 h ischemia induced by a rubber band tourniquet applied on the root of the hindlimb followed by reperfusion without (IR, n = 11) or after ACEi (n = 14; captopril 40 mg/kg per day during 28 days before surgery) were studied and compared to that of sham-operated animals (n = 11). The effect of ACEi on the non-ischemic contralateral leg was also determined in the ACEi group. Maximal oxidative capacities (Vmax) and complexes I, II and IV activities of the mitochondrial respiratory chain of the gastrocnemius muscle were determined using glutamate-malate, succinate and TMPD-ascorbate substrates. Arterial blood pressure was significantly decreased after ACEi (124 ± 2.8 vs. 108 ± 4.19 mmHg; P = 0.01). Ischemia-reperfusion reduced Vmax (4.4 ± 0.4 vs. 8.7 ± 0.5 μmol O2/min/g dry weight, -49%, P < 0.001), affecting mitochondrial complexes I, II and IV activities. ACEi failed to modulate ischemia-induced dysfunction (Vmax 5.1 ± 0.7 μmol O2/min/g dry weight) or the non-ischemic contralateral muscle respiratory rate. Ischemia-reperfusion significantly impaired the mitochondrial respiratory chain I, II and IV complexes of skeletal muscle. Pharmacologic pre-treatment with ACEi did not prevent or increase such alterations. Further studies might be useful to improve the pharmacologic conditioning of PAD patients needing arterial revascularization.

Original languageEnglish (US)
Pages (from-to)333-340
Number of pages8
JournalFundamental and Clinical Pharmacology
Issue number3
StatePublished - Jun 2010


  • ACE inhibition
  • Ischemia-reperfusion
  • Mitochondria
  • Muscle
  • Peripheral arterial disease
  • Renin-angiotensin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'Effect of chronic pre-treatment with angiotensin converting enzyme inhibition on skeletal muscle mitochondrial recovery after ischemia/reperfusion'. Together they form a unique fingerprint.

Cite this