Dietze Guenther J, Henriksen Erik J
Hypertension and Diabetes Research Unit, Max Grundig Clinic, Buehl, Germany.
J Renin Angiotensin Aldosterone Syst. 2008 Jun;9(2):75-88. doi: 10.3317/jraas.2008.011.
Recent evidence suggests a coordinated regulation by the local renin-angiotensin system (RAS) and tissue kallikrein-kinin system (TKKS) of blood flow and substrate supply in oxidative red myofibres of skeletal muscle tissue during endurance exercise. The performance of these myofibres is dependent on the increased oxidation of substrates facilitated by augmenting nutritive blood flow and glucose uptake. Humoral factors released by the contracting fibres, such as adenosine and kinins, are suggested to be responsible for this metabolic adjustment. The considerable drain of blood volume and the enormous consumption of glucose during endurance exercise require a control mechanism for the maintenance of blood pressure (BP) and glucose homeostasis. This is achieved by the sympathetic nervous system and its subordinate RAS, which is located in the nutritive vessels and parenchyma of the red myofibres. The angiotensin-converting enzyme (ACE) is the primary enzyme responsible for kinin degradation during exercise, underscoring the important interrelationship between the RAS and the TKKS in the critical role of kinins in the multifactorial regulation of muscle bioenergetics and glucose and BP homeostasis. Importantly, overactivity of the ACE, as occurs in individuals displaying risk factors such as overweight, causes exaggerated BP response and reduced glucose disposal. If they persist over years, compensatory responses to this ACE overactivity, such as hypersecretion of insulin and compliance of the vessel walls, will inevitably be exhausted, leading ultimately to the manifestation of type 2 diabetes and hypertension. This concept also provides a unifying explanation for the beneficial effects of ACE-inhibitors and Angiotensin II receptor antagonists in the treatment of hypertension and insulin resistance.
最近的证据表明，在耐力运动期间，局部肾素-血管紧张素系统（RAS）和组织激肽释放酶-激肽系统（TKKS）对骨骼肌组织氧化型红色肌纤维中的血流和底物供应进行协调调节。这些肌纤维的性能取决于通过增加营养性血流和葡萄糖摄取促进的底物氧化增加。收缩纤维释放的体液因子，如腺苷和激肽，被认为是这种代谢调节的原因。耐力运动期间大量的血容量消耗和葡萄糖的大量消耗需要一种维持血压（BP）和葡萄糖稳态的控制机制。这是通过交感神经系统及其下属的RAS实现的，RAS位于红色肌纤维的营养血管和实质中。血管紧张素转换酶（ACE）是运动期间负责激肽降解的主要酶，这突出了RAS和TKKS之间的重要相互关系，即激肽在肌肉生物能学以及葡萄糖和血压稳态的多因素调节中的关键作用。重要的是，ACE过度活跃，如在超重等具有风险因素的个体中发生的情况，会导致血压反应过度和葡萄糖处理减少。如果这些情况持续数年，对这种ACE过度活跃的代偿反应，如胰岛素分泌过多和血管壁顺应性，将不可避免地耗尽，最终导致2型糖尿病和高血压的表现。这一概念也为ACE抑制剂和血管紧张素II受体拮抗剂在治疗高血压和胰岛素抵抗方面的有益作用提供了统一的解释。
