Angiotensin-converting enzymes in skeletal muscle: Sentinel of blood pressure control and glucose homeostasis

Guenther J. Dietze, Erik J. Henriksen

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)75-88
Number of pages14
JournalJRAAS - Journal of the Renin-Angiotensin-Aldosterone System
Issue number2
StatePublished - Jun 2008


  • Angiotesin- converting enzymes
  • Diabetes
  • Endothellal derived
  • Hypertension
  • Hypolarizing factor
  • Kinins
  • Nitric oxide
  • Skeletal muscle contraction

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology


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