Does ACE inhibition enhance endurance performance and muscle energy metabolism in rats?
The renin-angiotensin-aldosterone system plays an important role in the hydroelectrolytic balance, blood pressure regulation, and cell growth. In some studies, the insertion (I) allele of the angiotensin-converting enzyme (ACE) gene, associated with a lower ACE activity, has been found in excess frequency in elite endurance athletes, suggesting that decreased ACE activity could be involved in endurance performance (Myerson S, Hemingway H, Budget R, Martin J, Humphries S, and Montgomery H. J Appl Physiol 87: 1313-1316, 1999). To test this hypothesis, we evaluated whether ACE inhibition could be associated with improved endurance performance and muscle oxidative capacity in rats. Eight male Wistar rats were treated for 10-12 wk with an ACE inhibitor, perindopril (2 mg.kg-1.day-1), and compared with eight control rats. Endurance time was measured on a treadmill, and oxidative capacity and regulation of mitochondrial respiration by substrates were evaluated in saponin-permeabilized fibers of slow soleus and fast gastrocnemius muscles. Endurance time did not differ between groups (57 +/- 5 min for perindopril vs. 55 +/- 6 min for control). Absolute and relative (to body weight) left ventricular weight was 20% (P < 0.01) and 12% (P < 0.01) lower, respectively, in the treated group. No difference in oxidative capacity, mitochondrial enzyme activities, or mitochondrial regulation by ADP was observed in soleus or gastrocnemius. Mitochondrial respiration with glycerol 3-phosphate was 17% higher in gastrocnemius (P < 0.03) and with octanoylcarnitine 14% greater in soleus (P < 0.01) of treated rats. These results demonstrate that ACE inhibition was not associated with improved endurance time and maximal oxidative capacity of skeletal muscles. This suggests that ACE activity has no implication in endurance capacity and only minor effects on mitochondrial function in sedentary animals.
Bahi
L
L
Cardiologie Cellulaire et Moléculaire, Institut National de la Santé et de la Recherche Médicale unité-446, 92296 Châtenay-Malabry, France.
Koulmann
N
N
Sanchez
H
H
Momken
I
I
Veksler
V
V
Bigard
A X
AX
Ventura-Clapier
R
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D020913:Perindopril / Q000494:pharmacology*; D010807:Physical Endurance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril