Angiotensin II induced catabolic effect and muscle atrophy are redox dependent

Abstract

Angiotensin II (Ang II) causes skeletal muscle wasting via an increase in muscle catabolism. To determine whether the wasting effects of Ang II were related to its ability to increase NADPH oxidase-derived reactive oxygen species (ROS) we infused wild-type C57BL/6J or p47phox−/− mice with vehicle or Ang II for 7 days. Superoxide production was increased 2.4 fold in the skeletal muscle of Ang II infused mice, and this increase was prevented in p47phox−/− mice. Apocynin treatment prevented Ang II-induced superoxide production in skeletal muscle, consistent with Ang II increasing NADPH oxidase derived ROS. Ang II induced loss of body and skeletal muscle weight in C57BL/6J mice, whereas the reduction was significantly attenuated in p47phox−/− animals. The reduction of skeletal muscle weight caused by Ang II was associated with an increase of proteasome activity, and this increase was completely prevented in the skeletal muscle of p47phox−/− mice. In conclusion, Ang II-induced skeletal muscle wasting is in part dependent on NADPH oxidase derived ROS.

Differential regulation of Na+transporters along nephron during ANG II-dependent hypertension: distal stimulation counteracted by proximal inhibition

“…As summarized in Table 3, ANG II infusion had the following effects: increased MAP measured from the carotid artery, increased heart weight, reduced rate of weight gain as reported previously (37), increased overnight urine volume Ͼ3-fold and increased urinary Na ϩ , K ϩ and osmolar excretion indicative of chronic pressurenatriuresis and diuresis. Kaliuresis and increased solute excretion could be attributed to the reduced skeletal muscle mass (37) or increased food consumption (not measured). Interestingly, ANG II infusion significantly reduced plasma [Na ϩ ], likely associated with the dipsogenic effects of ANG II (39), which is also reflected in the threefold increase in urine volume.…”

AT1 receptor-mediated augmentation of angiotensinogen, oxidative stress, and inflammation in ANG II-salt hypertension

“…ANG II has been shown to cause skeletal muscle wasting (cachexia) via an increase in muscle catabolism, associated with an increase in proteasome activity mediated, at least in part, by NADPH oxidase-derived ROS (39). Furthermore, ANG II infusion leads to decreases in body mass with decreases in retroperitoneal and epididymal fat but with no alterations in food consumption (34).…”

“…The oxidative fluorescent dye dihydroethidium (DHE; Invitrogen, Carlsbad, CA) was used to detect ROS in kidney poles from NS, ANG II, HS, ANG IIϩHS, and ANG IIϩHSϩARB rats, as previously described (39,41). Ten-micrometer cryosections from kidney poles, were stained with the superoxidesensitive dye DHE (10 mol/l) in a light-protected and humidified chamber for 30 min at 37°C.…”

Apocynin inhibits the upregulation of TGF-β1 expression and ROS production induced by TGF-β in skeletal muscle cells

“…Our data show that the expression of atrogin-1, an E3 ligase involved in skeletal muscle atrophy, is induced by TGF-β1 and also modulated by ROS in skeletal muscle cells. Thus, the participation of ROS seems to be a good candidate to evaluate, since its involvement in skeletal muscle atrophy induced by disuse or other causes has been suggested (Kondo et al, 1993;Semprun-Prieto et al, 2011).…”