Rouyer Olivier, Zoll Joffrey, Daussin Frederic, Damgé Christiane, Helms Pauline, Talha Sami, Rasseneur Laurence, Piquard Francois, Geny Bernard
Physiology Institute and CHRU-Strasbourg, 1 PL de l'Hôpital, Strasbourg 67091, France.
Exp Physiol. 2007 Nov;92(6):1047-56. doi: 10.1113/expphysiol.2007.038851. Epub 2007 Aug 3.
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.
由于运动能力与骨骼肌中的线粒体呼吸速率相关，且这两个参数都可能受到糖尿病的发生以及血管紧张素转换酶（ACE）抑制的调节，因此我们研究了慢性链脲佐菌素诱导的糖尿病（STZ）大鼠的骨骼肌氧化功能和运动能力是否受损，以及ACE抑制是否可以逆转这些异常情况。将ACE抑制剂培哚普利（2 mg kg⁻¹ 天⁻¹）给予7月龄的STZ大鼠5周（DIA - PE，n = 8），将其血流动力学功能、骨骼肌线粒体功能和运动能力与未治疗的糖尿病大鼠（DIA，n = 8）和对照大鼠（CONT，n = 8）进行比较。与CONT相比，DIA组的动脉血压升高（157 ± 12对130 ± 6 mmHg，P < 0.05），运动能力降低（分别为29 ± 2对91 ± 2分钟，P < 0.01）。与CONT大鼠相比，DIA组腓肠肌的氧化能力显著降低（分别为5.4 ± 0.5对10.6 ± 0.7 μmol O₂ min⁻¹（g干重）⁻¹，P < 0.001）。此外，DIA组中氧化与磷酸化之间的偶联显著受损（-52%，P < 0.001）。血管紧张素转换酶抑制（ACEi）使血压恢复正常，但未改善线粒体功能（DIA - PE大鼠为4.3 ± 0.8 μmol O₂ min⁻¹（g干重）⁻¹），反而使运动能力降低至更低水平（10 ± 1分钟，P < 0.01）。在DIA - PE组中，运动能力与血压呈正相关（r = 0.79，P < 0.05）。在实验性1型糖尿病大鼠中，骨骼肌线粒体呼吸和运动能力均受损。ACEi未能恢复肌肉功能，反而使运动能力恶化。进一步的研究将有助于确定平均全身血压降低继发的肌肉血流量不足是否可以解释这些结果。
