The superoxide dismutase mimetic tempol does not alleviate glucocorticoid‐mediated rarefaction of rat skeletal muscle capillaries

Autor: Erin R. Mandel, Emily C. Dunford, Ghoncheh Abdifarkosh, Patrick C. Turnbull, Christopher G. R. Perry, Michael C. Riddell, Tara L. Haas
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Physiological Reports, Vol 5, Iss 10, Pp n/a-n/a (2017)
Druh dokumentu: article
ISSN: 2051-817X
DOI: 10.14814/phy2.13243
Popis: Abstract Sustained elevations in circulating glucocorticoids elicit reductions in skeletal muscle microvascular content, but little is known of the underlying mechanisms. We hypothesized that glucocorticoid‐induced oxidative stress contributes to this phenomenon. In rats that were implanted with corticosterone (CORT) or control pellets, CORT caused a significant decrease in muscle glutathione levels and a corresponding increase in protein carbonylation, an irreversible oxidative modification of proteins. Decreased endothelial nitric oxide synthase and increased endothelin‐1 mRNA levels were detected after 9 days of CORT, and blood flow to glycolytic muscles was diminished. Control and CORT rats were treated concurrently with drinking water containing the superoxide dismutase mimetic tempol (172 mg/L) or the α‐1 adrenergic receptor antagonist prazosin (50 mg/L) for 6 or 16 days. Both tempol and prazosin alleviated skeletal muscle protein carbonylation. Tempol failed to prevent CORT‐mediated capillary rarefaction and was ineffective in restoring skeletal muscle blood flow. In contrast, prazosin blocked capillary rarefaction and restored skeletal muscle blood flow to control levels. The failure of tempol to prevent CORT‐induced skeletal muscle microvascular rarefaction does not support a dominant role of superoxide‐induced oxidative stress in this process. Although a decrease in protein carbonylation was observed with prazosin treatment, our data suggest that the maintenance of skeletal muscle microvascular content is related more closely with counteracting the CORT‐mediated influence on skeletal muscle vascular tone.
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