Effect of angiotensin‐converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin‐induced diabetic rats

Abstract

Since exercise capacity is related to the mitochondrial respiration rate in skeletal muscle and both parameters are potentially modulated by the onset of diabetes and by inhibition of the angiotensin-converting enzyme (ACE), we investigated whether skeletal muscle oxidative functions and exercise capacities are impaired in chronic streptozotocin-induced diabetic (STZ) rats and whether ACE inhibition could reverse such abnormalities. The ACE inhibitor perindopril (2 mg kg −1 day −1 ) was given for a period of 5 weeks to 7-month-old STZ rats (DIA-PE, n = 8) whose haemodynamic function, skeletal muscle mitochondrial function and exercise capacity were compared with those of untreated diabetic (DIA, n = 8) and control rats (CONT, n = 8). Increased arterial blood pressure (157 ± 12 versus 130 ± 6 mmHg, P < 0.05) and reduced exercise capacity (29 ± 2 versus 91 ± 2 min, respectively, P < 0.01) were observed in DIA compared with CONT. The oxidative capacity of the gastrocnemius muscle was significantly reduced in DIA compared with CONT rats (5.4 ± 0.5 versus 10.6 ± 0.7 µmol O 2 min −1 (g dry weight)−1 , respectively, P < 0.001). Moreover, the coupling between oxidation and phosphorylation was significantly impaired in DIA (−52%, P < 0.001). Angiotensin-converting enzyme inhibition (ACEi) normalized blood pressure without improving mitochondrial function (4.3 ± 0.8 µmol O 2 min −1 (g dry weight) −1 in DIA-PE rats) but reduced exercise capacity to even lower levels (10 ± 1 min, P < 0.01). Exercise capacity correlated positively with blood pressure in DIA-PE (r = 0.79, P < 0.05). In experimental type 1 diabetic rats, both skeletal muscle mitochondrial respiration and exercise capacity are impaired. The ACEi failed to restore the muscular function and worsened exercise capacity. Further studies will be useful to determine whether an inadequate muscular blood flow secondary to the reduction in mean systemic blood pressure can explain these results.

Polyphenols prevent ageing‐related impairment in skeletal muscle mitochondrial function through decreased reactive oxygen species production

“…Mitochondrial dysfunction might be a key factor in the ageing‐related decrease in skeletal muscle function. Indeed, mitochondria are the main energy producers in cells, and significant mitochondrial dysfunction leads to organ dysfunction (Fink, 2001; Rouyer et al 2007). In the present study, the use of main substrates allowed us to determine the mitochondrial respiratory chain complex activities precisely.…”

Long‐term hyperglycaemia decreases gastrocnemius susceptibility to permeability transition

“…As stated, several studies reported decreased muscle mitochondrial metabolism and morphological disturbances in STZ‐treated rats, including decreased mitochondrial mass, increased number of disarrayed cristae and mitochondrial swelling, reduced matrix electron density and compromised activity of several Krebs Cycle enzymes [5–9]. Mitochondrial alterations associated with decreased function seem to be related with increased oxidative stress and damage within the muscle from hyperglycaemic subjects [9].…”

Decreased muscle ACE activity enhances functional response to endurance training in rats, without change in muscle oxidative capacity or contractile phenotype

“…Prolonged ACE inhibition completely prevented the decreased skeletal muscle oxidative capacity expected in patients with chronic heart failure (10) and in rats with heart failure secondary to myocardial infarction (32,35). However, this protective effect of ACE inhibition remains controversial, and perindopril administration failed to restore muscle oxidative capacity and mitochondrial function in a rat model of heart failure induced by aortic stenosis (16) or in a rat model of type I diabetes (22). Taken together, these previous findings suggested that ACE inhibitors at best improve the mitochondrial dysfunction that characterizes skeletal muscle myopathy associated with chronic diseases.…”