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Abstract: Objective: This study was conducted to evaluate the relationship between hearing and cochlear histopathology after arginine vasopressin administration in rats. Methods: A total of 30 Wistar rats were injected with either 0.02unit/g of arginine vasopressin or the same amount of isotonic saline solution. The initial auditory brain stem response threshold was recorded and additional measurements were made at 10, 30, 60, and 90min after injection of arginine vasopressin or isotonic saline solution. The threshold for each timepoint was compared with the initial threshold. Histological quantitative assessment of endolymphatic hydrops in the cochlea was performed using light microscopy and assessment of the basal, intermediate, and marginal cells of the stria vascularis was performed with electron microscopy. Results: The auditory brain stem threshold 60min after arginine vasopressin injection increased significantly in comparison with the initial threshold (P <0.05). Although the index for endolymphatic hydrops in rats administered arginine vasopressin was not different from that in controls (P >0.05), vacuoles in the intermediate cells were increased significantly in the treated rats (P <0.01). Conclusion: Hearing impairment was detected without endolymphatic hydrops in rats administered arginine vasopressin. An increase of vacuoles in the intermediate cells may account for the hearing impairment induced by arginine vasopressin injection. [Copyright &y& Elsevier]

Atrial natriuretic peptide (ANP) is known to influence NaCl transport in the medullary thick ascending limbs (MAL), where the largest NaCl reabsorption occurs among distal nephron segments in response to arginine vasopressin (AVP). In the present study, we investigated the effect of ANP on bicarbonate (HCO3−) transport in the MAL using an isolated tubule perfusion technique. The HCO3− concentration was measured using free-flow ultramicro-fluorometer. We first observed basal HCO3− reabsorption in both long- and short-looped MALs (lMALs, and sMALs, respectively). AVP inhibited HCO3− reabsorption in both lMALs and sMALs, whereas ANP did not change HCO3− transport. However, in the presence of AVP, ANP restored the HCO3− reabsorption inhibited by AVP both in lMAL and sMAL. The effects of ANP on HCO3− transport was mimicked by cyclic GMP. The mRNA expression level of the vasopressin V2 receptor in lMALs was significantly higher than in sMALs, whereas expression of the V1a receptor was unchanged. In summary, AVP inhibits HCO3− transport, and ANP counteracts the action of AVP on HCO3− transport both in lMALs and sMALs. [ABSTRACT FROM AUTHOR]

Background: Vasopressin V1a receptor (V1aR) null mice have insufficient acid–base balance, but the target cell for V1aR signaling which results in the urinary acidification has not been identified. Methods: By using a quantitative in situ hybridization technique and a double-staining technique with an anti-AQP3 antibody in mice, we investigated the axial distribution and acidosis-induced expression of V1aR mRNA along the nephron. We also investigated the acidosis-induced morphological change in the tubule cells from wild-type and V1aR-null (V1aR −/−) mice. Results: In the normal condition, V1aR mRNA was moderately expressed in the medullary thick ascending limb (MTAL) and highly expressed in the intercalated cell (IC) throughout the collecting duct (CD). However, no expression was observed in the proximal tubule, thin limbs of Henle’s loop, and the principal cell of the CD. Importantly, V1aR mRNA was upregulated significantly both in the TAL and the IC of the CD in the inner stripe of the outer medulla (MTAL is and IC of OMCD is, respectively) when mice were treated with NH 4Cl (0.28 mol/L) for 6 days. Acidosis-induced hypertrophy, which was completely attenuated in V1aR −/− mice, was observed only in the IC of OMCD is ( P < 0.005). In addition, urinary excretion of ammonia (NH 3/NH 4+) was significantly decreased on day 3 ( P < 0.05) and day 6 ( P < 0.005) in the V1aR −/− mice treated with NH 4Cl. Conclusion: In conclusion, the IC of OMCD is may be the target cell stimulated by the vasopressin V1aR axis and contribute to urinary acidification, at least during metabolic acidosis. [ABSTRACT FROM AUTHOR]

The neuropeptide hormone arginine-vasopressin (AVP) is well known to exert its antidiuretic effect via the vasopressin V2 receptor (V2R), whereas the role of the vasopressin V1a receptor (V1aR) in the kidney remains to be clarified. Previously, we reported decreased plasma volume and blood pressure in Via receptor-deficient (V1aR) mice (Koshimizu T, Nasa Y, Tanoue A, Oikawa R, Kawahara Y, Kiyono Y, Adachi T, Tanaka T, Kuwaki T, Mon T. Proc Natl Acad Sci USA 103: 7807-78 12, 2006). In this study, we investigated the role of V1aR in urine concentration, renal function, and the renin-angiotensin system (RAS) using V1aR-/- mice. Urine volume of V1aR-/- mice was greater than that of wild-type mice, particularly when water was loaded, while the glomerular filtration rate (GFR), urinary NaCl excretion, AVP-dependent cAMP generation, V2R, and aquaporin 2 (AQP2) expression in the kidney were lower, indicating that the diminished GFR and V2R-AQP2 system led to impaired urinary concentration in V1aR-/- mice. Since the GFR and V2R-AQP2 system are regulated by RAS, we analyzed renin and angiotensin II in V1aR-/- mice and found that the plasma renin and angiotensin II were decreased. The expression of renin in granule cells was decreased in V1aR-/- mice, which led to a decreased level of plasma renin. In addition, the expression of renin stimulators such as neuronal nitric oxide synthase and cyclooxygenase-2 in macula densa (MD) cells, where V1aR was specifically expressed, was decreased in V1aR-/- mice. These data indicate that AVP regulates body fluid homeostasis and GFR via the V1aR in MD cells by activating RAS and subsequently the V2R-AQP2 system. [ABSTRACT FROM AUTHOR]

Sodium reabsorption via Na-K-2Cl cotransporter 2 (NKCC2) in the thick ascending limbs has a major role for medullary osmotic gradient and subsequent water reabsorption in the collecting ducts. We investigated intrarenal localization of three isoforms of NKCC2 mRNA expressions and the effects of dehydration on them in rats. To further examine the mechanisms of dehydration, the effects of hyperosmolality on NKCC2 mRNA expression in microdissected renal tubules was studied. RT-PCR and RT-competitive PCR were employed. The expressions of NKCC2a and b mRNA were observed in the cortical thick ascending limbs (CAL) and the distal convoluted tubules (DCT) but not in the medullary thick ascending limbs (MAL), whereas NKCC2f mRNA expression was seen in MAL and CAL. Two-day dehydration did not affect these mRNA expressions. In contrast, hyperosmolality increased NKCC2 mRNA expression in MAL in vitro . Bradykinin dose-dependently decreased NKCC2 mRNA expression in MAL. However, dehydration did not change NKCC2 protein expression in membrane fraction from cortex and outer medulla and in microdissected MAL. These data show that NKCC2a/b and f types are mainly present in CAL and MAL, respectively. Although NKCC2 mRNA expression was stimulated by hyperosmolality in vitro , NKCC2 mRNA and protein expressions were not stimulated by dehydration in vivo . These data suggest the presence of the inhibitory factors for NKCC2 expression in dehydration. Considering the role of NKCC2 for the countercurrent multiplier system, NKCC2f expressed in MAL might be more important than NKCC2a/b. [ABSTRACT FROM AUTHOR]