Impaired urinary concentrating ability in genetically polyuric mice.
Newly recognized strain of mice with hereditary polyuria (PUS mice) was characterized. Polyuria was inherited as a single autosomal-recessive trait. At 15 weeks, PUS mice excreted hypotonic (urine osmolality: PUS;270.8 +/- 15.5 vs. cont.; 3,228.6 +/- 163.6 mosm/kg) polyuria (urine volume: PUS; 25.0 +/- 1.5 vs. cont.; 1.1 +/- 0.1 ml/day). In PUS mice, plasma osmolality was slightly elevated as well as urinary excretion of vasopressin (AVP). Although PUS mice could concentrate urine after 24 h water deprivation, urine osmolality remained low. Blunted response to continuous infusion of dDAVP, a synthetic V2 agonist, was also observed. These in vivo studies indicated renal resistance to AVP contributed to the polyuria in this strain of mice. Microanalysis of isolated tubular segments revealed that AVP-induced cAMP accumulation in cortical collecting ducts (CCD) of PUS mice was significantly lower (60%) with or without a phosphodiesterase inhibitor, IBMX. Vasopressin induced similar cAMP accumulation in medullary ascending limbs of Henle (MAL), and medullary collecting ducts (MCD) between PUS and control mice. In CCDs, PUS mice had low basal adenylate cyclase (AdC) activity and responded less to AVP and forskolin stimulation than control mice. No difference in cyclic AMP phosphodiesterase activity was detected between control and PUS mice. These results indicate that impaired cAMP accumulation due to low AdC activity may be related to the impaired renal concentrating ability observed in this new strain of mice.
Homma
Sumiko
S
Department of Nephrology, Jichi Medical School, Minamikawachi, Tochigi, Japan. sumiho@jichi.ac.jp
Takeda
Sigeyuki
S
Kusano
Eiji
E
Matsuo
Yoshiyuki
Y
Shimizu
Toshikatsu
T
Nakamura
Masuhisa
M
Oohara
Tadao
T
Makino
Susumu
S
Asano
Yasushi
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001835:Body Weight; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004326:Drinking; D005260:Female; D007671:Kidney Concentrating Ability; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009994:Osmolar Concentration; D011141:Polyuria / Q000235:genetics* / Q000503:physiopathology*
D001127:Arginine Vasopressin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases