Pretreatment with brain natriuretic peptide reduces skeletal muscle mitochondrial dysfunction and oxidative stress after ischemia-reperfusion

Abstract

Brain natriuretic peptide (BNP) reduces the extent of myocardial infarction. We aimed to determine whether BNP may reduce skeletal muscle mitochondrial dysfunctions and oxidative stress through mitochondrial K(ATP) (mK(ATP)) channel opening after ischemia-reperfusion (IR). Wistar rats were assigned to four groups: sham, 3-h leg ischemia followed by 2-h reperfusion (IR), pretreatment with BNP, and pretreatment with 5-hydroxydecanoic acid, an mK(ATP) channel blocker, before BNP. Mitochondrial respiratory chain complex activities of gastrocnemius muscles were determined using glutamate-malate (V(max)), succinate (V(succ)), and N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride ascorbate (V(TMPD/asc)). Apoptosis (Bax-to-Bcl2 mRNA ratio and caspase-3 activity) and oxidative stress (dihydroethidium staining) were also assessed. Compared with the sham group, IR significantly decreased V(max), reflecting complex I, II, and IV activities (-36%, 3.7 ± 0.3 vs. 5.8 ± 0.2 μmol O(2)·min(-1)·g dry wt(-1), P < 0.01), and V(TMPD/asc), reflecting complex IV activity (-37%, 8.6 ± 0.8 vs. 13.7 ± 0.9 μmol O(2)·min(-1)·g dry wt(-1), P < 0.01). IR increased Bax-to-Bcl2 ratio (+57%, 1.1 ± 0.1 vs. 0.7 ± 0.1, P < 0.05) and oxidative stress (+45%, 9,067 ± 935 vs. 6,249 ± 723 pixels, P > 0.05). BNP pretreatment reduced the above alterations, increasing V(max) (+38%, P < 0.05) and reducing Bax-to-Bcl2 ratio (-55%, P < 0.01) and oxidative stress (-58%, P < 0.01). BNP protection against deleterious IR effects on skeletal muscles was abolished by 5-hydroxydecanoic acid. Caspase-3 activities did not change significantly. Conversely, BNP injected during ischemia failed to protect against muscle injury. In addition to maintaining the activity of mitochondrial respiratory chain complexes and possibly decreasing apoptosis, pretreatment with BNP protects skeletal muscle against IR-induced lesions, most likely by decreasing excessive production of radical oxygen species and opening mK(ATP) channels.

Effect of hyperoxic and hyperbaric conditions on the adenosinergic pathway and CD26 expression in rat

“…Besides its role in the immune response, there are various ways by which CD26 may participate in controlling the response to hyperoxia. First, a diminished degradation of CD26 substrate peptides with antioxidant capacity promotes their activity, which represents an obvious advantage in hyperoxic conditions (5,32,44,49,60). For example, a decreased degradation of the vasoactive intestinal peptide is consistent with the observation that its serum level increases following production of reactive oxygen species, which constitutes an adaptive response because the peptide has per se antioxidative capacities via its capacity to scavenge singlet oxygen and to reduce hydroxyl radical production (5,32,41,44).…”

Electroacupuncture pretreatment induces tolerance against cerebral ischemia/reperfusion injury through inhibition of the autophagy pathway

“…In addition, according to the results of a previous study, 'Baihui acupoint (GV20)'-stimulation with a density-sparse wave of 2/15 Hz and an intensity of 1 mA for 30 min/day over five consecutive days was reported to induce cerebral I/R tolerance (32). Evidence has suggested that I/R disturbs energy metabolism, increases oxidative stress and triggers apoptotic cell death (33). Previous studies have reported that EA pretreatment exerted neuroprotective effects against I/R injury via regulation of oxidative stress, maintenance of blood-brain barrier integrity and inhibition of apoptosis via various receptors (34,35).…”

Levels of brain natriuretic peptide are associated with peripheral arterial disease in subjects with type-2 diabetes mellitus

“…They also have beneficial effects in T2DM with PAD because natriuretic peptides can promote angiogenesis, modify the function of vascular endothelial cells, reduce cardiac load, and improve blood supply to the legs owing to their diuretic and vasodilatory effects [35-37]. In Wistar rats, pretreatment with BNP can attenuate the excessive production of radical oxygen species [38]. Various studies have indicated that BNP has aprotective role in vascular disease, butour data support the notion that higher BNP levels predispose to PAD development in T2DM.…”