title: Does angiotensin-converting enzyme inhibition improve the energetic status of cardiac and skeletal muscles in heart failure induced by aortic stenosis in rats?
abstract: Recently, we have demonstrated that heart failure in rats is associated with a myopathy altering energy metabolism in different muscles, but the origin of this myopathy is still unknown. Here, we studied the possible involvement of increased angiotensin II (Ang II) by treatment with perindopril, an inhibitor of angiotensin-converting enzyme (ACE). The beneficial effects of ACE inhibition could result either from vasodilatation-induced cardiac unloading or from inhibition of the direct angiotensin action on the muscle cells. The model of aortic banding with persisting left ventricular (LV) overload where the cardiac unloading does not occur allows to distinguish between the two effects of ACE inhibition. Four months after aortic clipping (just before the treatment), echocardiographic study showed an impairment of the systolic function (decrease of the LV shortening by 30% and ejection fraction by 21%). Ten-week treatment with perindopril dramatically decreased Ang II plasma level but did not reduce LV hypertrophy though a significant decrease in right ventricular (RV) hypertrophy occurred. Perindopril did not improve alterations in activities of energy metabolism enzymes (creatine kinase, citrate synthase, cytochrome c oxidase, lactate dehydrogenase) either in ventricular or in skeletal (gastrocnemius) muscle. Similarly, ACE inhibition did not improve the main parameters of mitochondrial respiration in permeabilized muscle fibers. These data suggest that the generalized metabolic myopathy induced by the hemodynamic abnormalities conditioned by the continuous LV overload (aorta clipping) does not result from the increase in Ang II level per se. Correction of hemodynamic parameters and LV unloading seem to be the prerequisite for the improvement of muscle energy metabolism abnormalities.
authors.affiliation: U-446 INSERM, Faculté de Pharmacie, Université Paris-XI, 92296, Châtenay-Malabry, France.
authors.forename: Iman
authors.initials: I
authors.lastname: Momken
authors.forename: Jules
authors.initials: J
authors.lastname: Kahapip
authors.forename: Lahoucine
authors.initials: L
authors.lastname: Bahi
authors.forename: Thierry
authors.initials: T
authors.lastname: Badoual
authors.forename: Luc
authors.initials: L
authors.lastname: Hittinger
authors.forename: Renée
authors.initials: R
authors.lastname: Ventura-Clapier
authors.forename: Vladimir
authors.initials: V
authors.lastname: Veksler
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000378:metabolism*; D001824:Body Constitution; D002303:Cardiac Output, Low / Q000378:metabolism*; D004452:Echocardiography; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D007703:Peptidyl-Dipeptidase A