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  • Franzén, Stephanie,1987-Linköpings universitet,Avdelningen för läkemedelsforskning,Centrum för medicinsk bildvetenskap och visualisering, CMIV,Experimentell Njurmedicin (author)

Intrarenal activation of endothelin type B receptors improve intrarenal oxygenation in type 1 diabetic rats

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  • LIBRIS-ID:oai:DiVA.org:liu-125525
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-125525URI

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  • Language:English

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  • About one third of patients with type 1 diabetes develop kidney damage. The mechanism is largely unknown, but intrarenal hypoxia has been proposed as a unifying mechanism for chronic kidney disease including diabetic nephropathy. The endothelin system has recently been demonstrated to regulate oxygen availability in the diabetic kidney via a pathway involving endothelin type A receptors (ETA-R). These receptors mainly mediate vasoconstriction and tubular sodium retention, and inhibition of ETA-R improves intrarenal oxygenation in the diabetic kidney. Endothelin type B receptors (ETB-R) have been reported to have opposite effects on vascular tone and tubular sodium handling. However, the role of ETB-R in kidney oxygen homeostasis is unknown.The effects of acute intrarenal ETB-R activation (Sarafotoxin 6c for 30-40 minutes; 0.78 pmol h-1 directly into the renal artery) on kidney function and oxygen metabolism were investigated in normoglycemic control and insulinopenic male Sprague Dawley rats administered streptozotocin (55 mg kg-1) two weeks before the acute experiments.Intrarenal activation of ETB-R improved oxygenation of the hypoxia diabetic kidney. However, neither effects on the diabetes-induced increased kidney oxygen consumption nor alterations in parameters related to tubular sodium transport could explain the improved oxygenation in the diabetic kidney after ETB-R activation. Rather, the improved kidney oxygenation was due to hemodynamic effects increasing oxygen delivery.In conclusion, increased ETB-R signaling in the diabetic kidney improves tissue oxygenation due to increased oxygen delivery as a result of increased total renal blood flow.

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  • Fasching, Angelica (author)
  • Palm, FredrikLinköpings universitet,Avdelningen för läkemedelsforskning,Centrum för medicinsk bildvetenskap och visualisering, CMIV(Swepub:liu)frepa35 (author)
  • Linköpings universitetAvdelningen för läkemedelsforskning (creator_code:org_t)

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Franzén, Stephan ...
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Palm, Fredrik
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MEDICAL AND HEALTH SCIENCES
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and Basic Medicine
and Physiology
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Linköping University

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