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Effect of angiotensin-converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats.
Exp Physiol. 2007 Nov; 92(6):1047-56.EP

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 micromol 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 micromol 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.

Authors+Show Affiliations

Physiology Institute and CHRU-Strasbourg, 1 PL de l'Hôpital, Strasbourg 67091, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17675412

Citation

Rouyer, Olivier, et al. "Effect of Angiotensin-converting Enzyme Inhibition On Skeletal Muscle Oxidative Function and Exercise Capacity in Streptozotocin-induced Diabetic Rats." Experimental Physiology, vol. 92, no. 6, 2007, pp. 1047-56.
Rouyer O, Zoll J, Daussin F, et al. Effect of angiotensin-converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats. Exp Physiol. 2007;92(6):1047-56.
Rouyer, O., Zoll, J., Daussin, F., Damgé, C., Helms, P., Talha, S., Rasseneur, L., Piquard, F., & Geny, B. (2007). Effect of angiotensin-converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats. Experimental Physiology, 92(6), 1047-56.
Rouyer O, et al. Effect of Angiotensin-converting Enzyme Inhibition On Skeletal Muscle Oxidative Function and Exercise Capacity in Streptozotocin-induced Diabetic Rats. Exp Physiol. 2007;92(6):1047-56. PubMed PMID: 17675412.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of angiotensin-converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats. AU - Rouyer,Olivier, AU - Zoll,Joffrey, AU - Daussin,Frederic, AU - Damgé,Christiane, AU - Helms,Pauline, AU - Talha,Sami, AU - Rasseneur,Laurence, AU - Piquard,Francois, AU - Geny,Bernard, Y1 - 2007/08/03/ PY - 2007/8/7/pubmed PY - 2007/12/14/medline PY - 2007/8/7/entrez SP - 1047 EP - 56 JF - Experimental physiology JO - Exp Physiol VL - 92 IS - 6 N2 - 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 micromol 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 micromol 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. SN - 0958-0670 UR - https://www.unboundmedicine.com/medline/citation/17675412/Effect_of_angiotensin_converting_enzyme_inhibition_on_skeletal_muscle_oxidative_function_and_exercise_capacity_in_streptozotocin_induced_diabetic_rats_ L2 - https://doi.org/10.1113/expphysiol.2007.038851 DB - PRIME DP - Unbound Medicine ER -