YoonWha Oh

Indomethacin Enhances Shuttling of Aquaporin-2 Despite Decreased Abundance in Rat Kidney

The effect of nonsteroidal antiinflammatory drugs on the regulation of aquaporin-2 (AQP2) water channels in the kidney was determined. Male Sprague-Dawley rats were injected with indomethacin (5 mg/kg twice a day intraperitoneally) for 2 d. The control group was injected with vehicle. The expression of AQP2 proteins was determined in the kidney by immunoblotting and immunohistochemistry. The expression of G(salpha) and type VI adenylyl cyclase was determined by immunoblotting. The activity of adenylyl cyclase complexes was determined by stimulated accumulation of cAMP. Immunoblotting revealed that indomethacin markedly decreased the expression of AQP2. Accordingly, however, the ratio of AQP2 expression in the membrane fraction versus that in the cytoplasmic fraction was increased. The urinary excretion of AQP2 proteins also increased. Immunohistochemistry demonstrated almost exclusive apical labeling of AQP2 with scanty cytoplasmic localization along the collecting duct. The expression of G(salpha) and adenylyl cyclase VI proteins was decreased. The generation of cAMP provoked by arginine vasopressin, sodium fluoride, or forskolin was blunted. These results suggest that indomethacin increases the shuttling of AQP2 while it decreases its abundance in the collecting duct.

Increased Expression of Renal Aquaporin Water Channels in Spontaneously Hypertensive Rats

Aims: The present study was aimed to determine whether there exists an altered regulation of aquaporin (AQP) water channels in hypertension. Methods: Male spontaneously hypertensive rats (SHR) aged 10–12 weeks were used. Age-matched Wistar-Kyoto (WKY) rats served as control. The abundance of AQP1–4 proteins in the kidney was determined by Western blot analysis. The protein expression and activity of adenylyl cyclase were also determined. Results: The medullary expression of AQP2 and AQP3 proteins was increased in SHR compared with that in WKY rats. The expression of AQP1 protein was also significantly increased in the inner medulla, while that of AQP4 was not. Immunohistochemistry of AQP2 revealed that principal cells of the collecting duct have strong immunoreactivity, the degree of which was augmented with prominent apical labeling in SHR. The plasma level of arginine vasopressin (AVP) was higher in SHR; the adenylyl cyclase activity stimulated by AVP was augmented, along with increased expression of type VI adenylyl cyclase. The urine was more concentrated with its volume decreased in SHR. Conclusion: The expression of AQP1–3 channels is increased in the kidney, in association with enhanced activity of the AVP/cAMP pathway, in SHR.

Caffeine Decreases The Expression of Na+/K+-Atpase and the Type 3 Na+/H+ Exchanger In Rat Kidney

1. The aim of the present study was to explore the mechanisms underlying the renal effects of caffeine.

Upregulation of vascular renin-angiotensin and endothelin systems in rats inhibited of nitric oxide synthesis.

The present study was aimed at investigating whether the regulation of vascular renin-angiotensin and endothelin (ET) systems is altered by a chronic blockade of nitric oxide (NO) synthesis. Male Sprague-Dawley rats were supplemented with N(G)-nitro-L-arginine methyl ester (L-NAME, 100mgl(-1)) in drinking water for 4 weeks to inhibit the endogenous synthesis of NO. The mRNA expressions of renin, angiotensin converting enzyme (ACE), type-1 angiotensin II receptor (AT1R), ET-1, type-A ET receptor (ET(A)), and neutral endopeptidase (NEP) were determined in the thoracic aorta by reverse transcription-polymerase chain reaction. The treatment with L-NAME significantly increased the blood pressure, while it decreased the tissue levels of nitrite/nitrate. The mRNA expression of renin, ACE, and AT1R was increased in the aorta. The protein expression of AT1R assessed by Western blot analysis was also increased. The expression of ET-1 and ET(A) mRNA was increased, whereas that of NEP mRNA decreased. The increased expression of renin-angiotensin and ET system genes and the decreased expression of NEP may in part be causally related with the development of hypertension induced by a chronic blockade of NO synthesis.

Altered Expression Of Vascular Natriuretic Peptide Receptors In Experimental Hypertensive Rats

1. The aim of the present study was to determine whether the regulation of vascular natriuretic peptide receptors (NPR) is related to the local renin–angiotensin system (RAS).

Diminished Expression of Sodium Transporters in the Ureteral Obstructed Kidney in Rats

Background/Aims: Whether the postobstructive natriuresis and diuresis is related with an altered regulation of sodium transporters in the kidney was examined. Methods: Male Sprague-Dawley rats underwent either bilateral (BUO) or unilateral obstruction (UUO) of the proximal ureters for 24 h. The expression of Na,K-ATPase, type-3 sodium-hydrogen exchanger (NHE3), type-1 bumetanide-sensitive sodium cotransporter (BSC1), and thiazide-sensitive sodium cotransporter (TSC) proteins was determined in the obstructed kidney by Western blot analysis and immunohistochemistry. Catalytic activity of Na,K-ATPase was also determined. Results: The expression of α1 and β1 subunit proteins and the catalytic activity of Na,K-ATPase were significantly decreased in the obstructed kidney in BUO. The expressions of NHE3, BSC1 and TSC proteins were also significantly decreased. Immunohistochemistry confirmed the downregulation of these sodium transporters in the obstructed kidney. In UUO, the expression of sodium transporters was similarly decreased in the obstructed kidney. Conclusion: The postobstructive natriuresis and diuresis may in part be accounted for by a reduced abundance of sodium transporters in the kidney.

Indomethacin decreases particulate guanylyl cyclase activity in rat kidney

1. Effects of non‐steroidal anti‐inflammatory drugs on the local atrial natriuretic peptide (ANP) and nitric oxide (NO) systems in the kidney were investigated.