Kidney international
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Reduced renal blood flow (RBF) is considered central to the pathogenesis of septic acute renal failure (ARF). However, no controlled experimental studies have continuously assessed RBF during the development of severe septic ARF. We conducted a sequential animal study in seven female Merino sheep. ⋯ After 24 h, urine output decreased from 1.4 to 0.3 ml/kg/h (P<0.05). Infusion of E. coli induced hyperdynamic sepsis and ARF. Septic ARF in this setting was associated with a marked increase in RBF and with renal vasodilatation.
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Kidney international · Jun 2006
Angiotensin-(1-7) inhibits angiotensin II-stimulated phosphorylation of MAP kinases in proximal tubular cells.
Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE, which is not blocked by ACE inhibitors. High amounts of ACE2 are present in the proximal tubule, and ACE2 catalyzes generation of angiotensin 1-7 (Ang-(1-7)) by this segment. Ang-(1-7) binds to a receptor distinct from the AT1 or AT2 Ang II receptor, identified as the mas receptor. ⋯ Ang-(1-7) had no significant effect on cyclic 3',5'-adenosine monophosphate production in these cells. In summary, Ang-(1-7) inhibits Ang II-stimulated MAPK phosphorylation in proximal tubular cells. Generation of Ang-(1-7) by proximal tubular ACE2 could thereby serve a protective role by counteracting the effects of locally generated Ang II.