Angiotensin II, Oxidative Stress and Skeletal Muscle Wasting

Abstract

Muscle atrophy (cachexia) is a muscle wasting syndrome associated with several pathological conditions in humans such as congestive heart failure, diabetes, AIDS, cancer and renal failure, and the presence of cachexia worsens outcome. Many of the conditions associated with cachexia are accompanied by stimulation of the reninangiotensin system and elevation in angiotensin II (ang II) levels. Ang II infusion induces skeletal muscle atrophy in rodents and mechanisms include increased expression of the E3 ligases atrogin-1/MuRF-1, an elevated rate of ubiquitin-proteasome mediated proteolysis and increased reactive oxygen species (ROS) levels, closely mimicking conditions of human cachexia. Ang II-induced oxidative stress contributes to muscle atrophy in a mouse model. Nicotinamide adenine dinucleotide phosphate oxidase- and mitochondria-derived ROS contribute to ang II-induced oxidative stress. Specific targeting of ROS and nicotinamide adenine dinucleotide phosphate oxidase/mitochondria cross-talk could be a beneficial, novel therapy to treat cachexia.

The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

“…7 One factor that produces muscle atrophy is angiotensin II (Ang II). [8][9][10] In several tissues, including skeletal muscle, Ang II and Ang-(1-7) present opposite functions. [11][12][13][14] Related to this, a recent report described the effect of Ang-(1-7) as an anti-atrophic factor in skeletal muscle in Ang II-dependent and -independent models, such as in immobilization or sepsis.…”

Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase

“…This result lead us to hypothesize a possible role of angiotensin II (ANG II) signaling in ClC-1 channel modulation. ANG II is known for its actions in cardiovascular system and its involvement in heart disease; however, it has been claimed that ANG II exerts prooxidant, proinflammatory, and profibrotic action in several tissues, among which is skeletal muscle (13,69,73). Increasing evidence supports a key role of enhanced activation of systemic and local renin-angiotensin system (RAS) and ANG II in aberrant remodeling and wasting conditions of skeletal muscle, including muscular dystrophy (13,41,43,70).…”

“…Increasing evidence supports a key role of enhanced activation of systemic and local renin-angiotensin system (RAS) and ANG II in aberrant remodeling and wasting conditions of skeletal muscle, including muscular dystrophy (13,41,43,70). Other than in microvasculature, the presence of ANG II receptors type 1 (AT 1 ) and 2 (AT 2 ) in myofibers and muscle cell lines has been described, although controversy is still unresolved about the role of these tissue receptors in mediating the ANG II actions in mature skeletal muscle (41,43,45,69,78). Importantly, ANG II via AT 1 receptor activates canonical G q protein PLC/PKC signaling, which also leads to activation of NADPH-oxidase (NOX) in most of the tissues where AT 1 receptors are expressed.…”

Exercise Intolerance in Chronic Heart Failure

“…13,19, 74 In addition, angiotensin II mediates muscle atrophy. 77 Increased sympathetic nerve activation (SNA), another important feature of CHF, contributes to peripheral vasoconstriction and limits skeletal muscle blood flow during rest and ex- Figure 3. Therapeutic implications and potential therapeutic tools for exercise intolerance in chronic heart failure.…”