2 system plays a key role in urine concentration in dehydration. In contrast to the upregulation of aquaporin 2, the downregulation of the vasopressin V2 receptor in dehydration is known. We investigated the mechanisms of this downregulation in dehydration using reverse transcription-competitive polymerase chain reaction (RT-competitive PCR) and Western blot analysis. The incubation of microdissected inner medullary collecting ducts (IMCDs) in a hypertonic medium or with vasopressin stimulated V2 receptor mRNA and protein expression, showing that dehydration-induced hyperosmolality in renal medulla and increased plasma arginine vasopressin (AVP) concentration should upregulate V2 receptor. The presence of inhibitory factors on the V2 receptor in dehydration was suggested. Prostaglandin E2 (PGE2) is known to inhibit AVP-induced cAMP production and to increase production in dehydration. PGE 2 slightly stimulated V2 receptor mRNA expression in IMCD in vitro. However, PGE 2 inhibited V2 receptor mRNA expression in IMCD in the presence of 10 Ϫ9 M vasopressin. The blockade of PGE2 synthesis by indomethacin in dehydrated rats increased V2 receptor protein expression after 24 -48 h with an early increase in V2 receptor mRNA expression. In summary, these data suggest that increased production of PGE 2 in renal medulla plays a key role in the downregulation of V2 receptor in dehydration. V2 receptor; aquaporin 2; prostaglandin E2; inner medullary collecting duct THE MAIN ROLE of the kidney is to maintain body fluid homeostasis. The kidney is a target site of many hormones such as arginine vasopressin (AVP), endothelin, atrial natriuretic peptide (ANP), parathyroid hormone (PTH), glucagon, and aldosterone. AVP plays a key role in urine concentration in the case of dehydration (18). AVP has two types of receptors in the kidney, V1a and V2 receptors. V1a receptors mediate the vasopressor effects of AVP and are localized in renal vessels and in the thick ascending limbs and the collecting ducts (26,28,34). In contrast, V2 receptors mediate the antidiuretic action of AVP and are localized in the thick ascending limbs and the collecting ducts (9,16,25,34). In the collecting ducts, the V2 receptor is located in the basolateral membrane of principal cells, while V1a receptor is mainly in the luminal membrane of both principal and intercalated cells (9,25,33). Urine concentration is caused by the binding of AVP to the V2 receptor and by the subsequent activation of aquaporin-2 (AQP2) (13,14,19,23). The V2 receptor acts as Gs and stimulates adenylate cyclase. Nephrogenic diabetes insipidus is caused by an abnormality in the V2 receptor or AQP2 (20). AQP2 is present in the luminal membrane and intracellular vesicles of principal cells (22). The V1a receptor activates Gq/11 and subsequently phosphoinositide turnover (1).In dehydration, trafficking of AQP2 in the intracellular vesicles to the apical membrane occurs as a short-term regulation (23). In long-term regulation, the expression of AQP2 is stimulated in chronic dehydration (35...

The effect of olmesartan, an inverse angiotensin II type 1 receptor blocker (ARB), on oxidative stress in hemodialysis (HD) patients is not fully understood, and has not been widely investigated in vitro or in vivo.

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The amiloride-sensitive epithelial sodium channel (ENaC) plays a key role in sodium reabsorption in the collecting ducts. We examined ENaC mRNA distribution along the nephron and acute effects of vasopressin and hyperosmolality on ENaC mRNA expression. ENaC , , and mRNA expressions were observed in cortical, outer medullary and initial inner medullary collecting ducts (CCD, OMCD and iIMCD, respectively).

SUMMARY: Apoptosis is related to a particular phase of the pathogenesis of diabetic nephropathy. the aim of the study is to investigate if (and if so where in the kidney) apoptotic changes occur during the early stage of diabetes mellitus. the incidence of renal cell apoptosis and its related Bcl‐2 proteins was investigated in the early stage of streptozotocin‐induced diabetic rats, using histological sections as well as isolated nephron segments and high glucose treatments in vitro. Modulation of the induced changes with the angiotensin‐converting enzyme (ACE) inhibitor, temocapril, was also analysed. Reverse transcription (RT)‐competitive polymerase chain reaction and western blot analysis were used. Glucose caused an increase of Bax mRNA expression in glomeruli and in the proximal straight tubule (PST), but not in the inner medullary collecting duct (IMCD). Glucose induced a decrease (40%) of Bcl‐2 mRNA expression in PST but not in glomeruli or in IMCD. Western blotting showed an increase of Bax protein expression in PCT, PST, and medullary thick ascending limb (MAL), and a decrease of Bcl‐2 protein expression in PST in diabetic rats. the ratio of Bcl‐2 to Bax decreased in PCT and PST in diabetic rats. the terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end‐labelling (TUNEL) method revealed the presence of apoptotic cells in proximal tubules in diabetic rats. Short‐term administration of temocapril did not affect Bax and Bcl‐2 protein expression in PCT or PST of diabetic rats. In conclusion, high ambient glucose could directly induce apoptotic changes in proximal tubules but not in glomeruli or in distal tubules at the early stage of diabetes mellitus.