The role of nitric oxide in the expression of renal aquaporin 2 in a cirrhotic rat model: does an AVP-independent mechanism exist for the regulation of AQP2 expression?
The aquaporin (AQP) water channel is expected to play a decisive role of hyponatremia and water retention in cirrhotic patients. Despite the importance of the water channel, however, previous findings vary widely when it concerns AQP2 of the kidneys in subjects with cirrhosis. The purpose of this study was to investigate the expression of AQP2 in the distal renal tubule in cirrhosis, and the presence of the nitric oxide-AQP2 signaling pathway as a possible vasopressin-aquaporin-independent pathway. Sixty male Wister rats were assigned to six groups: (1) control; (2) TAA (thioacetamide); (3) TAA with nitric oxide donor; (4) TAA with nitric oxide inhibitor; (5) TAA with HMG CoA reductase inhibitor; (6) TAA with tetrahydrobiopterin. Immunohistochemical staining for AQP2, real-time polymerase chain reaction (PCR) for AQP2 and 3, citrulline assay, and renal cGMP concentration were measured. The AQP2-positivity of cirrhotic rats were higher than the controls (P < 0.05). The AQP2-positivity decreased in the nitric oxide donor group, but the proportion rose back up when the subjects were injected with the nitric oxide inhibitor (P < 0.05). The expression of AQP2 and AQP3 mRNA was also found to show an increase in the cirrhotic group as compared with the normal controls (P < 0.05). The cirrhotic group administered with nitric oxide donor showed a significant decline in the expression of the mRNA. The control group's cGMP concentration was lower than that of the cirrhotic group (P < 0.05), but a comparison of the two groups injected with nitric oxide modulators, such as statin and BH4, did not show significant differences in the cGMP concentration level. The expression of AQP2 of the kidneys increased in the cirrhotic rats. AQP2 had relations to the activity changes of nitric oxide synthetase.
Jun
Dae Won
DW
Department of Internal Medicine, Eulji Medical Center, Eulji University College of Medicine, Seoul, Korea.
Park
Jin Hee
JH
Park
Yoo Sin
YS
Kang
Ju-Seop
JS
Kim
Eun Kyung
EK
Kim
Kyung Tae
KT
Son
Byoung Kwan
BK
Kim
Seong Hwan
SH
Jo
Yun Ju
YJ
Park
Young Sook
YS
D000704:Analysis of Variance; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013853:Thioacetamide
D051399:Aquaporin 2; D012333:RNA, Messenger; D013853:Thioacetamide; D001708:Biopterins; D009569:Nitric Oxide; D019821:Simvastatin; C003402:sapropterin; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D019331:NG-Nitroarginine Methyl Ester