Journal
PHYSIOLOGICAL REPORTS
Volume 9, Issue 5, Pages -Publisher
WILEY
DOI: 10.14814/phy2.14766
Keywords
cardiac function; diabetic nephropathy; homoarginine; NOS3
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [DK-094930, DK-094930S1]
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Homoarginine supplementation demonstrated kidney and heart protection in diabetic nephropathy models independently of NOS3, potentially mediated by improving mitochondrial function.
Recently we showed that homoarginine supplementation confers kidney protection in diabetic mouse models. In this study we tested whether the protective effect of homoarginine is nitric oxide synthase-3 (NOS3)-independent in diabetic nephropathy (DN). Experiments were conducted in NOS3 deficient (NOS3(-/-)) mice and their wild type littermate using multiple low doses of vehicle or streptozotocin and treated with homoarginine via drinking water for 24 weeks. Homoarginine supplementation for 24 weeks in diabetic NOS3(-/-) mice significantly attenuated albuminuria, increased blood urea nitrogen, histopathological changes and kidney fibrosis, kidney fibrotic markers, and kidney macrophage recruitment compared with vehicle-treated diabetic NOS3(-/-) mice. Furthermore, homoarginine supplementation restored kidney mitochondrial function following diabetes. Importantly, there were no significant changes in kidney NOS1 or NOS2 mRNA expression between all groups. In addition, homoarginine supplementation improved cardiac function and reduced cardiac fibrosis following diabetes. These data demonstrate that the protective effect of homoarginine is independent of NOS3, which will ultimately change our understanding of the mechanism(s) by which homoarginine induce renal and cardiac protection in DN. Homoarginine protective effect in DN could be mediated via improving mitochondrial function.
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