Messenger RNA expressions of vasopressin system and aquaporin-2 in adriamycin-induced nephrotic rats and effects of astragalus membranaceus.
OBJECTIVE
To investigate the expressions of hypothalamic arginine vasopressin (AVP) mRNA, renal AVP V2 receptor mRNA, and AVP-dependent aquaporin-2 (AQP2) mRNA in rats with adriamycin-induced nephrotic syndrome. Effects of Chinese herb Astragalus membranaceus (AM) were also tested.


METHODS
Sprague-Dawley rats with four weeks of adriamycin-induced nephrotic syndrome (NS) were used in this study. Another group NS + AM was set to testify the effects of AM given 0.5 g/kg daily on NS. Hypothalamic AVP mRNA expression was examined by dot blot method. Reverse transcription polymerase chain reaction was applied for detection of renal cortical and medullary V2 receptor and AQP2 mRNA. The results were normalized by mRNA of glyceraldehyde-3-phosphate dehydrogenase from the same sample.


RESULTS
All rats receiving adriamycin presented typical nephrosis. No obvious difference in plasma osmolality was detected among NS, NS + AM, and normal control (NC) rats. Hypothalamic AVP mRNA expression was higher in NS rats than NC (53.59 +/- 5.49 vs 25.72 +/- 1.96, P < 0.01). AM completely reversed this up-regulated expression (21.88 +/- 1.25). In both cortex and medulla of the kidney, nephrotic rat had increased AVP V2 expressions by 169% and 55%, respectively, compared with normal control rat. The increment of expression of AQP2 mRNA was consistent with that of V2 receptor in NS rat. AM could partially however significantly correct these up-regulations of V2 and AQP2 mRNA expressions (P < 0.01).


CONCLUSIONS
The up-regulated mRNA expressions of hypothalamic AVP, renal V2 receptor and AQP2 might play a role in edema formation in adriamycin-induced nephrotic rats. AM exerts its therapeutical effects on nephrosis partially through this mechanism.
Ma
J
J
Division of Nephrology, Huashan Hospital, Shanghai Medical University, Shanghai 200040, China.
Fan
S
S
Chen
J
J
Gu
Y
Y
Lin
S
S
D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000096:biosynthesis*; D001127:Arginine Vasopressin / Q000096:biosynthesis* / Q000378:metabolism; D027885:Astragalus propinquus; D004317:Doxorubicin; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000096:biosynthesis*
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D004317:Doxorubicin