title: Effect of chronic pre-treatment with angiotensin converting enzyme inhibition on skeletal muscle mitochondrial recovery after ischemia/reperfusion.
abstract: 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 (V(max)) 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 V(max) (4.4 +/- 0.4 vs. 8.7 +/- 0.5 micromol O2/min/g dry weight, -49%, P < 0.001), affecting mitochondrial complexes I, II and IV activities. ACEi failed to modulate ischemia-induced dysfunction (V(max) 5.1 +/- 0.7 micromol 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.
authors.affiliation: Department of Vascular Surgery, Nouvel Hopital Civil, Strasbourg, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Thaveau
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
authors.forename: Jamal
authors.initials: J
authors.lastname: Bouitbir
authors.forename: Benoît
authors.initials: B
authors.lastname: N'guessan
authors.forename: Philippe
authors.initials: P
authors.lastname: Plobner
authors.forename: Nabil
authors.initials: N
authors.lastname: Chakfe
authors.forename: Jean-Georges
authors.initials: JG
authors.lastname: Kretz
authors.forename: Ruddy
authors.initials: R
authors.lastname: Richard
authors.forename: François
authors.initials: F
authors.lastname: Piquard
authors.forename: Bernard
authors.initials: B
authors.lastname: Geny
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D004334:Drug Administration Schedule; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors