American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Apr 2005
The role of NOS2 and NOS3 in renal protein and arginine metabolism during early endotoxemia in mice.
Previously, we observed an enhanced renal protein synthesis and increased de novo arginine production in the early response to endotoxemia in wild-type Swiss mice (Hallemeesch MM, Soeters PB, and Deutz NE. Am J Physiol Renal Physiol 282: F316-F323, 2002). To establish whether these changes are regulated by nitric oxide (NO) synthesized by NO synthase isoforms NOS2 and NOS3, we studied C57BL6/J wild-type (WT), NOS2-deficient (NOS2(-/-)), and NOS3-deficient (NOS3(-/-)) mice under baseline (unstimulated) and LPS-treated conditions. ⋯ Collectively, these data show that NOS2 is constitutively expressed in the kidney and remarkably functional as it affects renal blood flow and de novo arginine production under baseline conditions and is important for the increase in renal citrulline turnover during endotoxemia. NOS3, in contrast, appears less important for renal metabolism. The increase in renal protein turnover during endotoxemia does not depend on NOS2 or NOS3 activity.
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Am. J. Physiol. Renal Physiol. · Apr 2005
Angiotensin II AT1 receptor blockade decreases vasopressin-induced water reabsorption and AQP2 levels in NaCl-restricted rats.
Vasopressin and ANG II, which are known to play a major role in renal water and sodium reabsorption, are mainly coupled to the cAMP/PKA and phosphoinositide pathways, respectively. There is evidence for cross talk between these intracellular signaling pathways. We therefore hypothesized that vasopressin-induced water reabsorption could be attenuated by ANG II AT(1) receptor blockade in rats. ⋯ In conclusion, ANG II AT(1) receptor blockade in DDAVP-treated rats was associated with decreased urine concentration and decreased AQP2 and AQP1 expression. Moreover, FE(Na) was increased in parallel with decreased expression of NHE3, NCC, and Na-K-ATPase. These results suggest that ANG II AT(1) receptor activation plays a significant role in regulating aquaporin and sodium transporter expression and modulating urine concentration in vivo.
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Am. J. Physiol. Renal Physiol. · Apr 2005
Lithium treatment inhibits renal GSK-3 activity and promotes cyclooxygenase 2-dependent polyuria.
The use of LiCl in clinical psychiatry is routinely complicated by overt nephrogenic diabetes insipidus (NDI), the mechanism of which is incompletely understood. In vitro studies indicate that lithium can induce renal medullary interstitial cell cyclooxygenase 2 (COX2) protein expression via inhibition of glycogen synthase kinase-3beta (GSK-3beta). Both COX1 and COX2 are expressed in the kidney. ⋯ Lithium also decreased renal medullary GSK-3beta activity, and this was temporally related to increased COX2 expression in the kidney from lithium-treated mice, consistent with a tonic in vivo suppression of COX2 expression by GSK-3 activity. In conclusion, these findings temporally link decreased GSK-3 activity to enhanced renal COX2 expression and COX2-derived urine PGE(2) excretion. Suppression of COX2-derived PGE(2) blunts lithium-associated polyuria.