Sanches TR, Volpini RA, Massola Shimizu MH, de Bragança AC, Oshiro-Monreal F, Seguro AC, Andrade L. Sildenafil reduces polyuria in rats with lithium-induced NDI. Am J Physiol Renal Physiol 302: F216 -F225, 2012. First published October 12, 2011 doi:10.1152/ajprenal.00439.2010.-Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na ϩ /H ϩ exchanger 3 (NHE3), Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC2), epithelial Na channel (ENaC; ␣-, -, and ␥-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2-4, Sil (200 mg/kg food) or Li and Sil (LiϩSil). In LiϩSil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the LiϩSil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in LiϩSil rats, AQP2 expression was partially normalized, whereas that of UT-A1, ␥-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Liinduced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.aquaporin-2; diabetes insipidus; urea transporter; sodium transporters LITHIUM (Li) has been widely used as a pharmacological agent in psychiatric therapy and is the established drug of choice for treating bipolar affective disorders (20,21,29,31). It is eliminated primarily through renal excretion and competes with the Na-K-2Cl cotransporter (NKCC2) and the epithelial sodium channel (ENaC) (12,13,39). In addition, Li is transported by Na-K-ATPase (12,13,39). Approximately 60% of the filtered load of Li is reabsorbed in the proximal tubule, whereas 20% is reabsorbed in the thick ascending limb, connecting tubule, and cortical collecting duct (12, 13). Nephrogenic diabetes insipidus (NDI), increased urinary excretion of sodium (UVNa), and distal renal tubular acidosis have all been associated with Li treatment (16,17,22,31). In particular, Li-induced NDI is associated with dysregulation of aquaporin-2 (AQP2) and ENaC in the collecting duct (20,22,23,26,41). Furthermore, reduced urine concentrating ability has been shown to accompany decreased expression of th...
Background/Aims: Renal risks of nicotine exposure associated with hypercholesterolemia are still unknown. Methods: Thus, hypercholesterolemic rats (HC) and their control (C) were evaluated by inulin clearance (InCl) measured at baseline and during nicotine infusion (100 μg/kg b.w.). Five groups were studied: (i) C; (ii) DEN (C submitted to a renal denervation); (iii) C + L-arginine (0.25% in drinking water); (iv) HC, and (v) HC + L-arginine (0.25% in drinking water). Furthermore, C and HC had their renal blood flow (RBF) measured and they have also been chronically treated with nicotine (12.5 μg/ml in drinking water) to assess InCl on the 8th day. Results: Nicotine increased blood pressure in C, DEN and HC and reduced InCl only in C. L-Arginine treatment blunted nicotine effects on blood pressure and increased InCl only in C. Moreover, nicotine did not change RBF in C but elicited in HC, whereas renal vascular resistance was increased in C and unchanged in HC. Indeed, chronic nicotine exposure has also reduced InCl in C. Conclusion: Nicotine acted on the adrenergic system and nitric oxide counteracted this action in C, but the same may not be applied to HC. An impairment in renal autoregulation may explain why InCl was unchanged in HC.
Background/Aims: Hypomagnesemia may induce hypercholesterolemia, but the contrary has not been described yet. Thus, magnesium homeostasis was evaluated in rats fed a cholesterol-enriched diet for 8 days. This study has a relevant clinical application if hypomagnesemia, due to hypercholesterolemia, is confirmed in patients with long-term hypercholesterolemia. Methods: Both hypercholesterolemic (HC) and normocholesterolemic rats (NC) were divided into sets of experiments to measure hemodynamic parameters, physiological data, maximum capacity to dilute urine (CH2O), variations (Δ) in [Ca2+]i and the expression of transporter proteins. Results: HC developed hypomagnesemia and showed high magnesuria in the absence of hemodynamic abnormalities. However, the urinary sodium excretion and CH2O in HC was similar to NC. On the other hand, the responses to angiotensin II by measuring Δ [Ca2+]i were higher in the thick ascending limb of Henle’s loop (TAL) of HC than NC. Moreover, high expression of the cotransporter NKCC2 was found in renal outer medulla fractions of HC. Taken together, the hypothesis of impairment in TAL was excluded. Actually, the expression of the epithelial Mg2+ channel in renal cortical membrane fractions was reduced in HC. Conclusion: Impairment in distal convoluted tubule induced by hypercholesterolemia explains high magnesuria and hypomagnesemia observed in HC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.