Effect of primary polydipsia on aquaporin and sodium transporter abundance

2003 ◽  
Vol 285 (5) ◽  
pp. F965-F971 ◽  
Author(s):  
Melissa A. Cadnapaphornchai ◽  
Sandra N. Summer ◽  
Sandor Falk ◽  
Joshua M. Thurman ◽  
Mark A. Knepper ◽  
...  
Keyword(s):  
Water Deprivation ◽  
Molecular Mechanisms ◽  
Collecting Duct ◽  
Protein Abundance ◽  
Sprague Dawley ◽  
Water Metabolism ◽  
Urinary Osmolality ◽  
Primary Polydipsia ◽  
Sodium Transporter ◽  
Urinary Concentrating Ability

Chronic primary polydipsia (POLY) in humans is associated with impaired urinary concentrating ability. However, the molecular mechanisms responsible for this finding have not been elucidated. The purpose of this study was to examine the effect of chronic primary POLY on water metabolism and renal aquaporin (AQP) water channels and sodium and urea transporter abundance in rats. Primary POLY was induced in male Sprague-Dawley rats by daily administration of 15 g powdered rat chow mixed in 100 ml water for 10 days. Control rats (CTL) received 15 g powdered rat chow per day and ad libitum drinking water. Rats were studied following this period before further intervention and with a 36-h period of water deprivation to examine maximal urinary concentrating ability. At baseline, POLY rats demonstrated significantly greater water intake (100 ± 1 vs. 22 ± 2 ml/day, P < 0.0001) and urinary output (80 ± 1 vs. 11 ± 1 ml/day, P < 0.0001) and decreased urinary osmolality (159 ± 13 vs. 1,365 ± 188 mosmol/kgH2O, P < 0.001) compared with CTL rats. These findings were accompanied by decreased inner medulla AQP-2 protein abundance in POLY rats compared with CTL rats before water deprivation (76 ± 2 vs. 100 ± 7% CTL mean, P < 0.007). With water deprivation, maximal urinary osmolality was impaired in POLY vs. CTL rats (2,404 ± 148 vs. 3,286 ± 175 mosmol/kgH2O, P < 0.0005). This defect occurred despite higher plasma vasopressin concentrations and similar medullary osmolalities in POLY rats. In response to 36-h water deprivation, inner medulla AQP-2 protein abundance was decreased in POLY rats compared with CTL rats (65 ± 5 vs. 100 ± 5% CTL mean, P < 0.0006). No significant differences were noted in renal protein abundance of either AQP-3 or AQP-4 or sodium and urea transporters. We conclude that the impaired urinary concentrating ability associated with primary POLY in rats is due to impaired osmotic equilibration in the collecting duct that is mediated primarily by decreased AQP-2 protein abundance.

Lack of vasopressin-independent upregulation of AQP-2 gene expression in homozygous Brattleboro rats

1999 ◽  
Vol 277 (2) ◽  
pp. R427-R433 ◽  
Author(s):  
Takako Saito ◽  
San-E Ishikawa ◽  
Sei Sasaki ◽  
Minori Higashiyama ◽  
Shoichiro Nagasaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Water Deprivation ◽  
Collecting Duct ◽  
Renal Medulla ◽  
Brattleboro Rats ◽  
Severe Dehydration ◽  
Urinary Osmolality ◽  
Independent Mechanism ◽  
Collecting Duct Cells

Arginine vasopressin (AVP) plays an important role in the expression of aquaporin (AQP-2) in the collecting duct. The present study was undertaken to determine whether there is an AVP-independent regulation of AQP-2 gene expression in homozygous Brattleboro rats in which endogenous AVP is absent. Exogenous administration of 1-deamino-8-d-AVP produced an antidiuresis and expressed AQP-2 mRNA and AQP-2 protein in the renal medulla of the homozygous Brattleboro rats. Twelve hours of water deprivation produced severe dehydration in the homozygous Brattleboro rats, such that urinary osmolality increased from 200 to 649 mosmol/kgH2O. However, no increase in AQP-2 mRNA expression was observed after this dehydration, and the medullary tissue content and urinary excretion of AQP-2 also remained unchanged. Increases in AQP-2 mRNA expression and AQP-2 protein were evident in Long-Evans rats after 64 h of water deprivation, with a severity of dehydration almost equal to the 12-h dehydrated, homozygous Brattleboro rats. These results indicate the lack of an AVP-independent mechanism for upregulating AQP-2 mRNA expression in renal collecting duct cells.

Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality

2005 ◽  
Vol 288 (5) ◽  
pp. F912-F920 ◽  
Author(s):  
Yuqiang Ge ◽  
Dowahn Ahn ◽  
Peter K. Stricklett ◽  
Alisa K. Hughes ◽  
Masashi Yanagisawa ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Urine Volume ◽  
Urine Osmolality ◽  
Water Metabolism ◽  
Urinary Osmolality ◽  
Water Load ◽  
Endothelin 1 ◽  
Normal Water

In vitro studies suggest that endothelin-1 (ET-1) inhibits vasopressin (AVP)-stimulated water permeability in the collecting duct (CD). To evaluate the role of CD-derived ET-1 in regulating renal water metabolism, the ET-1 gene was selectively disrupted in the CD (CD ET-1 KO). During normal water intake, urinary osmolality (Uosm), plasma Na concentration, urine volume, and renal aquaporin-2 (AQP2) levels were unchanged, but plasma AVP concentration was reduced in CD ET-1 KO animals. CD ET-1 KO mice had impaired ability to excrete an acute, but not a chronic, water load, and this was associated with increased CD ET-1 mRNA in control, but not CD ET-1 KO, mice. In response to continuous infusion of 1-desamino-8-d-arginine vasopressin, CD ET-1 KO mice had greater increases in Uosm, V2 and AQP2 mRNA, and phosphorylation of AQP2. CD suspensions from CD ET-1 KO mice had enhanced AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ET-1 KO increases renal sensitivity to the urinary concentrating effects of AVP and suggest that ET-1 functions as a physiological autocrine regulator of AVP action in the CD.

E3 ubiquitin-protein ligases in rat kidney collecting duct: response to vasopressin stimulation and withdrawal

2011 ◽  
Vol 301 (4) ◽  
pp. F883-F896 ◽  
Author(s):  
Yu-Jung Lee ◽  
Jeong-Eun Lee ◽  
Hyo-Jung Choi ◽  
Jung-Suk Lim ◽  
Hyun Jun Jung ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Mass Spectrometry Analysis ◽  
Protein Abundance ◽  
Sprague Dawley ◽  
Spectrometry Analysis ◽  
Protein Ligases

The E3 ubiquitin (Ub)-protein ligases (E3s) play a role as regulators of protein trafficking and degradation. We aimed to integrate the profile of E3s in rat kidney and examine the changes in protein abundance of the selected E3s in response to 1-deamino-8-d-arginine vasopressin (dDAVP) stimulation/withdrawal. Sprague-Dawley rats were infused with vehicle ( n = 13), dDAVP for 5 days ( n = 13), or dDAVP was withdrawn for periods (15 min, 30 min, 1, 3, 6, 12, or 24 h) after 5-day infusion ( n = 46). Total RNA was isolated from the inner medulla (IM) for transcriptome analysis. Plasma membrane (PM)- or intracellular vesicle (ICV)-enriched fractions of whole kidney were immunoisolated for liquid chromatography-tandem mass spectrometry analysis. dDAVP infusion for 5 days (D5d) significantly increased urine osmolality, which was maintained during 3-h withdrawal of dDAVP after 5-day infusion (D5d-3h). Consistent with this, aquaporin-2 (AQP2) expression in the PM fractions of D5d and D5d-3h increased, whereas AQP2 expression in the ICV fractions of D5d-3h was further increased, indicating internalization of AQP2. Transcriptome analysis revealed 86 genes of E3s and LC-MS/MS analysis demonstrated 16 proteins of E3s. Among these, seven E3s (BRCA1, UBR4, BRE1B, UHRF1, NEDD4, CUL5, and FBX6) were shared. RT-PCR demonstrated mRNA expressions of the seven identified E3s in the kidney, and immunoblotting demonstrated changes in protein abundance of the selected E3s (BRE1B, NEDD4, and CUL5) in response to dDAVP stimulation/withdrawal or lithium-induced nephrogenic diabetes insipidus. The rate of AQP2 degradation was retarded in mpkCCDc14 cells with small interfering RNA-mediated knockdown of NEDD4 or CUL5. Taken together, identified E3s could be involved in the degradation of proteins associated with vasopressin-induced urine concentration.

scholarly journals Potential involvement of P2Y2 receptor in diuresis of postobstructive uropathy in rats

2010 ◽  
Vol 298 (3) ◽  
pp. F634-F642 ◽  
Author(s):  
Yue Zhang ◽  
Donald E. Kohan ◽  
Raoul D. Nelson ◽  
Noel G. Carlson ◽  
Bellamkonda K. Kishore
Keyword(s):  
Mrna Expression ◽  
Collecting Duct ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Urinary Concentration ◽  
Sham Operation ◽  
Protein Abundance ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Relative Mrna Expression

AVP resistance of the medullary collecting duct (mCD) in postobstructive uropathy (POU) has been attributed to increased production of PGE2. P2Y2 receptor activation causes production of PGE2 by the mCD. We hypothesize that increased P2Y2 receptor expression and/or activity may contribute to the diuresis of POU. Sprague-Dawley rats were subjected to bilateral ureteral obstruction for 24 h followed by release (BUO/R, n = 17) or sham operation (SHM/O, n = 15) and euthanized after 1 wk or 12 days. BUO/R rats developed significant polydipsia, polyuria, urinary concentration defect, and increased urinary PGE2 and decreased aquaporin-2 protein abundance in the inner medulla compared with SHM/O rats. After BUO/R, the relative mRNA expression of P2Y2 and P2Y6 receptors was increased by 2.7- and 4.9-fold, respectively, without significant changes in mRNA expression of P2Y1 or P2Y4 receptor. This was associated with a significant 3.5-fold higher protein abundance of the P2Y2 receptor in BUO/R than SHM/O rats. When freshly isolated mCD fractions were challenged with different types of nucleotides (ATPγS, ADP, UTP, or UDP), BUO/R and SHM/O rats responded to only ATPγS and UTP and released PGE2, consistent with involvement of the P2Y2, but not P2Y6, receptor. ATPγS- or UTP-stimulated increases in PGE2 were much higher in BUO/R (3.20- and 2.28-fold, respectively, vs. vehicle controls) than SHM/O (1.68- and 1.30-fold, respectively, vs. vehicle controls) rats. In addition, there were significant 2.4- and 2.1-fold increases in relative mRNA expression of prostanoid EP1 and EP3 receptors, respectively, in the inner medulla of BUO/R vs. SHM/O rats. Taken together, these data suggest that increased production of PGE2 by the mCD in POU may be due to increased expression and activity of the P2Y2 receptor. Increased mRNA expression of EP1 and EP3 receptors in POU may also help accentuate PGE2-induced signaling in the mCD.

scholarly journals Role for ovarian hormones in purinoceptor-dependent natriuresis

2020 ◽  
Author(s):  
Eman Gohar ◽  
Malgorzata Kasztan ◽  
Shali Zhang ◽  
Edward W Inscho ◽  
David M Pollock
Keyword(s):  
Mrna Expression ◽  
Collecting Duct ◽  
Premenopausal Women ◽  
Renal Medulla ◽  
Receptor Protein ◽  
Protein Abundance ◽  
Sprague Dawley ◽  
Ovx Rats ◽  
Downstream Effectors ◽  
Renal Tubular

Abstract Background: Premenopausal women have a lower risk of hypertension compared to age-matched men and postmenopausal women. P2Y2 and P2Y4 purinoceptor can be considered potential contributors to hypertension due to their emerging roles in regulating renal tubular Na+ transport. Activation of these receptors inhibits epithelial Na+ channel activity (ENaC) via a phospholipase C (PLC)-dependent pathway resulting in natriuresis. We recently reported that activation of P2Y2 and P2Y4 receptors in the renal medulla by UTP promotes natriuresis in male and ovariectomized (OVX) rats, but not in ovary-intact females. This led us to hypothesize that ovary-intact females have greater basal renal medullary activity of P2 (P2Y2 and P2Y4) receptors regulating Na+ excretion compared to male and OVX rats. Methods: To test our hypothesis, we determined (i) the effect of inhibiting medullary P2 receptors by suramin (750 μg/kg/min) on urinary Na+ excretion in anesthetized male, ovary-intact female and OVX Sprague Dawley rats, (ii) mRNA expression and protein abundance of P2Y2 and P2Y4 receptors and (iii) mRNA expression of their downstream effectors (PLC-1d and ENaCa) in renal inner medullary tissues obtained from these three groups. We also subjected cultured mouse inner medullary collecting duct cells (segment 3, mIMCD3) to different concentrations of 17ß-estradiol (E2, 0, 10, 100 and 1000 nM) to test whether E2 increases mRNA expression of P2Y2 and P2Y4 receptors.Results: Acute P2 inhibition attenuated urinary Na+ excretion in ovary-intact females, but not in male or OVX rats. We found that P2Y2 and P2Y4 mRNA expression was higher in the inner medulla from females compared to males or OVX. Inner medullary lysates showed that ovary-intact females have higher P2Y2 receptor protein abundance, compared to males, however, OVX did not eliminate this sex difference. We also found that E2 dose-dependently upregulated P2Y2 and P2Y4 mRNA expression in mIMCD3. Conclusion: These data suggest that ovary-intact females have enhanced P2Y2 and P2Y4-dependent regulation of Na+ handling in the renal medulla, compared to male and OVX rats. We speculate that the P2 pathway contributes to facilitated renal Na+ handling in premenopausal females.

A short water deprivation test incorporating urinary arginine vasopressin estimations for the investigation of posterior pituitary function in children

1988 ◽  
Vol 117 (1) ◽  
pp. 13-18 ◽  
Author(s):  
D. B. Dunger ◽  
J. R. Seckl ◽  
D. B. Grant ◽  
L. Yeoman ◽  
S. L. Lightman
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Nephrogenic Diabetes Insipidus ◽  
Water Deprivation ◽  
Posterior Pituitary ◽  
Urinary Osmolality ◽  
Water Drinking ◽  
Group A ◽  
Group B ◽  
Urinary Concentrating Ability

Abstract. The value of a 7-h water deprivation test incorporating urinary osmolality and urinary arginine vasopressin (AVP) measurements was investigated in 20 children with suspected anterior or posterior pituitary dysfunction (group A) and 11 presenting with polyuria and polydipsia (group B). A control group of 16 healthy children was also studied. Urinary osmolalities in the control subjects after 7 h of water deprivation were 827–1136 mosmol/kg and urinary AVP 114–320 pmol/l. Of the group A patients, 5 had symptomatic diabetes insipidus with urinary osmolalities < 300 mosmol/kg, and urinary AVP concentrations of < 10 pmol/l, and 5 had normal urinary concentrating ability. The other 10 patients had varying degrees of partial diabetes insipidus (urinary AVP 6–53 pmol/l) although in 3 urinary concentrating ability was well maintained (osmolality 650–747 mosmol/kg). In group B, a diagnosis of compulsive water drinking was made in 9 patients, 1 had nephrogenic diabetes insipidus (urinary osmolality 68 mosmol/kg, AVP 782 pmol/l), and the final patient had transient diabetes insipidus. The test described was easy to perform and well tolerated even in young children. Using this test alone, it was possible to identify patients with partial defects of posterior pituitary function even when urinary concentrating ability was maintained, as well as those with complete cranial diabetes insipidus, nephrogenic diabetes insipidus, and compulsive water drinking.

scholarly journals Effects of salt depletion on the kidney: changes in medullary oxygenation and thick ascending limb size.

1994 ◽  
Vol 4 (8) ◽  
pp. 1538-1545
Author(s):  
I E Stillman ◽  
M Brezis ◽  
S N Heyman ◽  
F H Epstein ◽  
K Spokes ◽  
...  
Keyword(s):  
Salt Intake ◽  
Collecting Duct ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Deficient Diet ◽  
Cross Sectional ◽  
Short Loop ◽  
Sprague Dawley Rats ◽  
Salt Depletion ◽  
Urinary Concentrating Ability

Previous studies have shown that salt depletion enhances the susceptibility of the kidney to nephrotoxins (amphotericin, cyclosporine, and contrast). To study the renal response to salt depletion, Sprague-Dawley rats were fed a sodium-deficient diet (N = 12) with pair-fed controls (N = 13) for 4 wk. In addition, rats from each group underwent 24-h water deprivation studies (N = 9; four salt deprived, five normal). Plastic 1-micron horizontal sections of mid-inner stripe were examined, and cross-sectional areas of the medullary thick ascending limb (mTAL) were analyzed. The mTAL of the salt-deprived rats were smaller (P = 0.04) and showed greater variance in size (P = 0.02) than control (618 +/- 106 versus 693 +/- 50 microns2). However, mean glomerular and collecting duct cross-sectional areas were unaffected by salt intake. Cross-sectional areas of long- and short-loop mTAL were significantly different, regardless of group (518 +/- 78 versus 732 +/- 92 microns2). Maximal urinary concentrating ability was found to correlate with mTAL cross-sectional area (r = 0.85; P = 0.004) and with long-loop mTAL size (r = 0.77; P = 0.016). However, it did not significantly correlate with short loop mTAL size (r = 0.53; P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Role for ovarian hormones in purinoceptor-dependent natriuresis

2020 ◽  
Author(s):  
Eman Gohar ◽  
Malgorzata Kasztan ◽  
Shali Zhang ◽  
Edward W Inscho ◽  
David M Pollock
Keyword(s):  
Mrna Expression ◽  
Collecting Duct ◽  
Premenopausal Women ◽  
Renal Medulla ◽  
Receptor Protein ◽  
Na Channel ◽  
Protein Abundance ◽  
Sprague Dawley ◽  
Ovx Rats ◽  
Renal Tubular

Abstract Background: Premenopausal women have a lower risk of hypertension compared to age-matched men and postmenopausal women. P2Y 2 and P2Y 4 purinoceptor can be considered potential contributors to hypertension due to their emerging roles in regulating renal tubular Na + transport. Activation of these receptors inhibits epithelial Na + channel activity (ENaC) via a phospholipase C (PLC)-dependent pathway resulting in natriuresis. We recently reported that activation of P2Y 2 and P2Y 4 receptors in the renal medulla by UTP promotes natriuresis in male and ovariectomized (OVX) rats, but not in ovary-intact females. This led us to hypothesize that ovary-intact females have greater basal renal medullary activity of P2 (P2Y 2 and P2Y 4 ) receptors regulating Na + excretion compared to male and OVX rats. Methods: To test our hypothesis, we determined (i) the effect of inhibiting medullary P2 receptors by suramin (750 μg/kg/min) on urinary Na + excretion in anesthetized male, ovary-intact female and OVX Sprague Dawley rats, (ii) mRNA expression and protein abundance of P2Y 2 and P2Y 4 receptors and (iii) mRNA expression of their downstream effectors (PLC-1d and ENaCa) in renal inner medullary tissues obtained from these three groups. We also subjectedcultured mouse inner medullary collecting duct cells (segment 3, mIMCD3) to different concentrations of 17ß-estradiol(E 2 , 0, 10, 100 and 1000 nM) to test whether E 2 increases mRNA expression of P2Y 2 and P2Y 4 receptors. Results: Acute P2 inhibition attenuated urinary Na + excretion in ovary-intact females, but not in male or OVX rats.We found that P2Y 2 and P2Y 4 mRNA expression was higher in the inner medulla from females compared to males or OVX. Inner medullary lysates showed that ovary-intact females have higher P2Y 2 receptor protein abundance, compared to males, however, OVX did not eliminate this sex difference. We also found that E 2 dose-dependently upregulated P2Y 2 and P2Y 4 mRNA expression in mIMCD3. Conclusion: These data suggest that females have enhanced P2Y 2 and P2Y 4 -dependent regulation of Na + handling in the renal medulla, compared to male and OVX rats. We speculate that the P2 pathway contributes to facilitated renal Na + handling in premenopausal females.

scholarly journals Role for ovarian hormones in purinoceptor-dependent natriuresis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Eman Y. Gohar ◽  
Malgorzata Kasztan ◽  
Shali Zhang ◽  
Edward W. Inscho ◽  
David M. Pollock
Keyword(s):  
Mrna Expression ◽  
Collecting Duct ◽  
Premenopausal Women ◽  
Renal Medulla ◽  
Receptor Protein ◽  
Protein Abundance ◽  
Sprague Dawley ◽  
Ovx Rats ◽  
Downstream Effectors ◽  
Renal Tubular

Abstract Background Premenopausal women have a lower risk of hypertension compared to age-matched men and postmenopausal women. P2Y2 and P2Y4 purinoceptor can be considered potential contributors to hypertension due to their emerging roles in regulating renal tubular Na+ transport. Activation of these receptors inhibits epithelial Na+ channel activity (ENaC) via a phospholipase C (PLC)-dependent pathway resulting in natriuresis. We recently reported that activation of P2Y2 and P2Y4 receptors in the renal medulla by UTP promotes natriuresis in male and ovariectomized (OVX) rats, but not in ovary-intact females. This led us to hypothesize that ovary-intact females have greater basal renal medullary activity of P2 (P2Y2 and P2Y4) receptors regulating Na+ excretion compared to male and OVX rats. Methods To test our hypothesis, we determined (i) the effect of inhibiting medullary P2 receptors by suramin (750 μg/kg/min) on urinary Na+ excretion in anesthetized male, ovary-intact female, and OVX Sprague Dawley rats, (ii) mRNA expression and protein abundance of P2Y2 and P2Y4 receptors, and (iii) mRNA expression of their downstream effectors (PLC-1δ and ENaCα) in renal inner medullary tissues obtained from these three groups. We also subjected cultured mouse inner medullary collecting duct cells (segment 3, mIMCD3) to different concentrations of 17ß-estradiol (E2, 0, 10, 100, and 1000 nM) to test whether E2 increases mRNA expression of P2Y2 and P2Y4 receptors. Results Acute P2 inhibition attenuated urinary Na+ excretion in ovary-intact females, but not in male or OVX rats. We found that P2Y2 and P2Y4 mRNA expression was higher in the inner medulla from females compared to males or OVX. Inner medullary lysates showed that ovary-intact females have higher P2Y2 receptor protein abundance, compared to males; however, OVX did not eliminate this sex difference. We also found that E2 dose-dependently upregulated P2Y2 and P2Y4 mRNA expression in mIMCD3. Conclusion These data suggest that ovary-intact females have enhanced P2Y2 and P2Y4-dependent regulation of Na+ handling in the renal medulla, compared to male and OVX rats. We speculate that the P2 pathway contributes to facilitated renal Na+ handling in premenopausal females.

scholarly journals Evidence for bradykinin as a stimulator of thirst

2004 ◽  
Vol 286 (5) ◽  
pp. F875-F880 ◽  
Author(s):  
Melissa A. Cadnapaphornchai ◽  
Boris Rogachev ◽  
Sandra N. Summer ◽  
Yung-Chang Chen ◽  
Lajos Gera ◽  
...  
Keyword(s):  
Water Intake ◽  
Urine Output ◽  
Urine Osmolality ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Protein Abundance ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Primary Polydipsia ◽  
Ad Libitum ◽  
Captopril Treatment

Angiotensin-converting enzyme inhibition (ACEI) with captopril has been shown to increase water intake and urine output in rats, but the mechanism is unknown. ACEI impairs the conversion of ANG I to ANG II, a dipsogenic hormone, and impairs the degradation of bradykinin. The goal of this study was to examine the role of bradykinin in the polydipsia and polyuria associated with ACEI. Male Sprague-Dawley rats received captopril (CPT; 20 mg·kg-1·day-1) in ground chow for 48 h. Water intake, food intake, and urine output were monitored and compared with control rats (CTL), rats receiving captopril treatment with limited water intake (CPT-LIM), and rats receiving captopril treatment with ad libitum water intake plus 24-h treatment with the bradykinin antagonist B-9430 (CPT-BK1). CPT rats consumed significantly more water and produced more urine vs. CTL. Urine osmolality was significantly decreased in CPT rats vs. CTL. Inner medullary aquaporin-2 (AQP2) protein abundance was also markedly decreased in CPT rats vs. CTL. These findings were reversed in CPT-LIM rats, suggesting captopril-induced primary polydipsia. CPT-BKI rats demonstrated parameters no different from CTL despite ad libitum water intake. Mean arterial pressure and 24-h creatinine clearance did not differ among groups. We conclude that ACEI with captopril induces primary polydipsia despite impaired production of the dipsogen ANG II and that this primary increase in water intake is likely the cause of the decreased protein abundance of inner medullary AQP2. Furthermore, this dipsogenic effect was reversed by antagonism of bradykinin, thus implicating this hormone in thirst regulation in the rat.

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