Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q92565 (GFR)
 4,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The mechanism underlying the antidiuretic effect of thiazide diuretics in diabetes insipidus (DI) is unknown. This study addressed two specific questions: is the reduction in urine flow rate (V) related to a decrease in the delivery of fluid from the pars recta of the proximal tubules ('distal delivery'), and are there any changes in the expression and/or intracellular distribution of vasopressin stimulated water channels (AQP2) in the collecting ducts, during chronic thiazide-induced antidiuresis? 2. Nine Brattleboro rats with vasopressin-deficient DI were treated for 5 days with bendroflumethiazide (BFTZ), 9 mg kg(-1) day(-1) orally, and 9 Brattleboro rats were left untreated. BFTZ-treated DI rats showed a fall in V from approximately 200 to approximately 75 ml day(-1) and an increase in urine osmolality from approximately 130 to approximately 400 mosmol kg(-1). 3. BFTZ-induced antidiuresis was associated with a persistent loss of sodium, but not of potassium. After 5 days of treatment, clearance studies in conscious rats showed a tendency towards decreases in effective renal plasma flow (-7%), GFR (-12%) and lithium clearance (C(Li); used as marker for distal delivery) (-25%), compared with untreated controls, but none of these changes were statistically significant. There was no apparent relationship between C(Li) and V in BFTZ-treated or untreated DI rats. 4. BFTZ treatment did not change the expression of AQP2 in homogenates of cortex, outer or inner medulla from DI rats, or from normal Long Evans rats. Light and electron microscopic immunocytochemistry revealed no changes in intracellular distribution of AQP2 in principal cells from inner medullary collecting ducts of BFTZ-treated DI rats. 5. We concluded, (i) that although the antidiuretic effect of BFTZ in rats with DI is associated with a net loss of Na, the decrease in V shows no association with changes in distal delivery, as estimated by C(Li). (ii) Antidiuretic treatment with BFTZ does not alter the expression of subcellular distribution of AQP2 water channels in the collecting ducts. The mechanism underlying the chronic antidiuresis caused by thiazide diuretics in DI remains elusive.
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PMID:Mechanism of antidiuresis caused by bendroflumethiazide in conscious rats with diabetes insipidus. 951 94

The renin-angiotensin system is well known to be involved in the pathophysiological changes in renal function after obstruction of the ureter. Previously, we demonstrated that bilateral ureteral obstruction (BUO) is associated with dramatic changes in the expression of both renal sodium transporters and aquaporin water channels (AQPs). We now examined the effects of the AT(1)-receptor antagonist candesartan on the dysregulation of AQPs and key renal sodium transporters in rats subjected to 24-h BUO and followed 2 days after release of BUO (BUO-2R). Consistent with previous observations, BUO-2R resulted in a significantly decreased expression of AQP1, -2, and -3 compared with control rats. Concomitantly, the rats developed polyuria and reduced urine osmolality. Moreover, expression of the type 2 Na-phosphate cotransporter (NaPi-2) and type 1 bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) was markedly reduced, consistent with postobstructive natriuresis. Candesartan treatment from the onset of obstruction attenuated the reduction in GFR (3.1 +/- 0.4 vs. 1.7 +/- 0.3 ml.min(-1).kg(-1)) and partially prevented the reduction in the expression of AQP2 (66 +/- 21 vs. 13 +/- 2%, n = 7; P < 0.05), NaPi-2 (84 +/- 6 vs. 57 +/- 10%, n = 7; P < 0.05), and NKCC2 (89 +/- 12 vs. 46% +/- 11, n = 7; P < 0.05). Consistent with this, candesartan treatment attenuated the increase in urine output (58 +/- 4 vs. 97 +/- 5 microl.min(-1).kg(-1), n = 7; P < 0.01) and the reduction in sodium reabsorption (433 +/- 62 vs. 233 +/- 45 micromol.min(-1).kg(-1), n = 7; P < 0.05) normally found in rats subjected to BUO. Moreover, candesartan treatment attenuated induction of cyclooxygenase 2 (COX-2) expression in the inner medulla, suggesting that COX-2 induction in response to obstruction is regulated by ANG II. In conclusion, candesartan prevents dysregulation of AQP2, sodium transporters, and development of polyuria seen in BUO. This strongly supports the view that candesartan protects kidney function in response to urinary tract obstruction.
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PMID:Angiotensin II mediates downregulation of aquaporin water channels and key renal sodium transporters in response to urinary tract obstruction. 1675 30

Unilateral ureteral obstruction (UUO) impairs function of the obstructed kidney, and the contralateral nonobstructed kidney compensates depending on the degree and duration of UUO. This study aimed to determine the hemodynamic and molecular changes in the solitary kidney in response to partial ureteral obstruction (PUO) where any compensation from the contralateral kidney was eliminated so that all observed changes in the kidney tissue occurred in the kidney with PUO. Newborn rats were subjected to unilateral left nephrectomy (UNX) within the first 48 h of life and a subset of UNX rats was subjected to severe PUO of the right kidney at day 14. Renal blood flow and whole kidney volume were measured with MRI at week 10. The renal protein abundance of aquaporin 1 (AQP1), AQP2 and AQP3 as well as Na,K-ATPase, NaPi-2 (type 2 sodium-phosphate cotransporter) and NHE3 (type 3 sodium-proton exchanger) were examined by immunoblotting and immunocytochemistry. At 10 weeks of age, the protein abundance of AQP2, AQP3, Na,K-ATPase, NaPi-2 and NHE3 were increased in response to PUO. In contrast, AQP1 expression was markedly decreased compared to sham-operated rats. These findings were confirmed by immunohistochemistry. GFR, urine osmolality and urine sodium excretion were reduced and kidney weight increased in response to PUO. In conclusion, the present study demonstrated major changes in the protein abundance of renal AQP1, AQP2 and AQP3 and sodium transporters in the solitary PUO kidney. These changes were paralleled by decreased urinary sodium excretion and a significant reduction in urinary osmolality from the obstructed kidney, suggesting a functional association between the molecular changes and the ability of the obstructed kidney to handle sodium and water in this solitary kidney model.
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PMID:Regulation of aquaporins and sodium transporter proteins in the solitary kidney in response to partial ureteral obstruction in neonatal rats. 2167 14